Publications by authors named "Qianwen Wang"

91 Publications

The role of sleep disorders in cardiovascular diseases: Culprit or accomplice?

Life Sci 2021 Jul 26:119851. Epub 2021 Jul 26.

Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China. Electronic address:

Sleep disorders frequently comorbid with several cardiovascular diseases (CVDs), attracting increasing scientific attention and interest. Sleep disorders include insomnia, sleep-disordered breathing, restless legs syndrome, etc. It is well known that inflammation, sympathetic activation, and endothelial dysfunction play critical roles in sleep disorders, all of which are predisposing factors for CVDs. The comorbidity of sleep disorders and CVDs may have a bidirectional relationship. Patients with CVDs may have a high incidence of sleep disorders and vice versa. This review focused on the comorbidity of sleep disorders and CVDs and discussed the potential pathophysiological mechanisms and therapeutic strategies. In addition to the existing mechanisms, this review summarized novel potential mechanisms underlying comorbidities, such as gut microbiota, orexin, and extracellular vesicles, which may provide a theoretical basis for further basic research and clinical investigations on improving therapeutic outcomes.
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http://dx.doi.org/10.1016/j.lfs.2021.119851DOI Listing
July 2021

Inflammation-Related circRNA Polymorphism and Ischemic Stroke Prognosis.

J Mol Neurosci 2021 Jul 17. Epub 2021 Jul 17.

Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.

CircRNAs belong to a novel class of noncoding RNAs that are generated by exons of genes by alternative mRNA splicing and involved in pathophysiological processes of ischemic stroke by regulating neuro-inflammation. A total of 982 patients were enrolled in our study for stroke recovery analysis. The aim of our study was to first explore the association between the inflammation-related circRNA polymorphism and functional outcome 3 months after ischemic stroke by using multivariate logistic regression model. Next, we further investigated the role of circRNA polymorphism in predicting stroke recurrence by using Cox proportional hazard regression model. Five circRNA polymorphisms were genotyped by using polymerase chain reaction and ligation detection reaction method. We identified circ-STAT3 (signal transducer and activator of transcription) rs2293152 GG genotype to be associated with poorer recovery 90 days after stroke (OR = 1.452, 95% CI: 1.165-4.362, p = 0.016). After adjusting for confound factors, the association for rs2293152 with 3 months outcome after IS was stronger, suggesting a mechanism that rs2293152 is an independent risk factor for stroke recovery (OR = 2.255, 95% CI: 1.034-2.038, p = 0.031). However, no other circRNA polymorphisms (circ-DLGAP4 rs41274714, circ-TRAF2 rs10870141, circ-ITCH rs10485505, rs4911154) were associated with functional outcome 3 months after stroke in any genetic models. Subgroup analysis revealed that the negative effect of rs2293152 GG genotype was greater in female and older patients, subjects with history of hypertension. Additionally, all the circRNA polymorphisms were not correlated with recurrent risk of ischemic stroke. Our results indicated that circ-STAT3 might be a novel biomarker for predicting functional outcome after stroke and an important contributor to the ischemic stroke recovery.
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http://dx.doi.org/10.1007/s12031-021-01889-5DOI Listing
July 2021

OncoThreads: visualization of large-scale longitudinal cancer molecular data.

Bioinformatics 2021 07;37(Suppl_1):i59-i66

Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.

Motivation: Molecular profiling of patient tumors and liquid biopsies over time with next-generation sequencing technologies and new immuno-profile assays are becoming part of standard research and clinical practice. With the wealth of new longitudinal data, there is a critical need for visualizations for cancer researchers to explore and interpret temporal patterns not just in a single patient but across cohorts.

Results: To address this need we developed OncoThreads, a tool for the visualization of longitudinal clinical and cancer genomics and other molecular data in patient cohorts. The tool visualizes patient cohorts as temporal heatmaps and Sankey diagrams that support the interactive exploration and ranking of a wide range of clinical and molecular features. This allows analysts to discover temporal patterns in longitudinal data, such as the impact of mutations on response to a treatment, for example, emergence of resistant clones. We demonstrate the functionality of OncoThreads using a cohort of 23 glioma patients sampled at 2-4 timepoints.

Availability And Implementation: Freely available at http://oncothreads.gehlenborglab.org. Implemented in Java Script using the cBioPortal web API as a backend.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275328PMC
July 2021

Effects of a Modified Tap Dance Program on Ankle Function and Postural Control in Older Adults: A Randomized Controlled Trial.

Int J Environ Res Public Health 2021 06 12;18(12). Epub 2021 Jun 12.

School of Sports Science and Physical Education, Nanjing Normal University, Nanjing 210023, China.

Older adults are at a high risk of falling due to age-related degradations in physical fitness. This study aimed to examine the effects of a modified tap dance program (MTD) on ankle function and postural control in older adults. Forty-four healthy older adults (mean age = 64.1 years, with 9 men) were recruited from local communities and were randomly divided into the MTD group and the control (CON) group. The MTD group received 12 weeks of MTD training 3 times per week for 30 min per session. Outcomes were measured using the five times sit-to-stand test (FTSST) for ankle strength, the universal goniometer for ankle range of motion, and the Footscan to trace the center of pressure. Results revealed significant improvements in FTSST in the MTD group (mean difference = 1.01), plantar flexion (left = 9.10, right = 10.0). In addition, the MTD group displayed significantly more improvements at midtest than the CON group in FTSST (mean difference = 1.51) and plantar flexion (mean difference: left = 6.10; right = 4.5). Therefore, the MTD can be an effective exercise program for ankle function improvement, but it has limited effects on improving postural control among healthy older adults.
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http://dx.doi.org/10.3390/ijerph18126379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296212PMC
June 2021

ABA regulation of root growth during soil drying and recovery can involve auxin response.

Plant Cell Environ 2021 Jun 27. Epub 2021 Jun 27.

Fujian Provincial Key Laboratory of Plant Functional Biology and College of Life Sciences, Joint International Research Laboratory of Water and Nutrient in Crop and College of Resources and Environment, Fujian Agriculture and Forestry University, Fuzhou, China.

Abscisic acid (ABA) plays an important role in plant adaptation to water deficits, but its role in regulating root growth (primary root elongation and lateral root number) during different drought-phases remains unclear. Here, we exposed wild-type (WT) and ABA-deficient (not) tomato plants to three continuous drought-phases (moderate drying: day 0-21; severe drying: day 22-47 and re-watering: day 48-51). It was found that WT increased primary root growth during moderate drying; maintained more lateral roots, and greater primary root and total root length under severe drying; and produced more roots after re-watering. After RNA-Seq analysis, we found that the auxin-related genes in root showed different expression patterns between WT and not under drying or re-watering. Further, exogenous supply of IAA partially recovered the root growth of ABA-deficient not plants under three continuous drought-phases. Our results suggested that ABA regulation of tomato root growth during soil drying and recovery can involve auxin response.
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http://dx.doi.org/10.1111/pce.14137DOI Listing
June 2021

Homocysteine and Folic Acid: Risk Factors for Alzheimer's Disease-An Updated Meta-Analysis.

Front Aging Neurosci 2021 26;13:665114. Epub 2021 May 26.

Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, China.

Recent studies have reported that homocysteine (Hcy) may play a vital role in the pathogenesis of vascular dementia (VaD) and Alzheimer's disease (AD). Our study explored the relationship between the plasma Hcy and folate levels and the risk of dementia. We searched Embase, PubMed, and Web of Science for published literature, including case-control studies and prospective cohort studies, and performed a systematic analysis. The results of our meta-analysis, consisting of case-control studies, showed higher levels of Hcy and lower levels of folate in dementia, AD, and VaD patients than those in non-demented controls (for dementia: SMD = 0.812, 95% CI [0.689, 0.936], = 0.000 for Hcy; SMD = -0.677, 95% CI [-0.828, -0.525], = 0.000 for folate). AD patients showed significantly lower plasma Hcy levels compared to VaD patients (SMD = -0.278, 95% CI [-0.466, -0.09], = 0.000). Subgroup analysis revealed that ethnicity, average age, and dementia type had no significant effect on this association. Furthermore, from the analysis of prospective cohort studies, we identified that elevated plasma Hcy levels were associated with an increased risk of dementia, AD, and VaD (RR = 1.22, 95% CI [1.08, 1.36]; RR = 1.07, 95% CI [1.04, 1.11]; RR = 1.13, 95% CI [1.04, 1.23]). In addition, every 5 μmol/L increase in the plasma Hcy level was associated with a 9% increased risk of dementia and a 12% increased risk of AD. Hcy and folic acid are potential predictors of the occurrence and development of AD. A better understanding of their function in dementia could provide evidence for clinicians to rationalize clinical intervention strategies.
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http://dx.doi.org/10.3389/fnagi.2021.665114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188894PMC
May 2021

Identifying key areas of imbalanced supply and demand of ecosystem services at the urban agglomeration scale: A case study of the Fujian Delta in China.

Sci Total Environ 2021 Jun 5;791:148173. Epub 2021 Jun 5.

School of Architecture, Tianjin University, Tianjin 300072, China.

The coordinated supply and demand of ecosystem services (ESs) is important for ensuring regional sustainable development. However, research identifying key areas of imbalanced supply and demand of ESs at the urban agglomeration scale is limited. Therefore, in this study, using the Fujian Delta urban agglomeration of China as the research area, based on multi-source data, and analysis tools, such as ArcGIS, ENVI, and GeoDa, we constructed a research framework and indicator system for ESs supply and demand to determine the spatial change law, matching degree, and coupling coordination degree (CCD) of the ESs. On this basis, the key areas of imbalanced supply and demand of ESs were identified, and optimization strategies were proposed. The results showed that (1) there is obvious spatial heterogeneity between ESs supply and demand in the study area, and different degrees of spatial changes occurred with urbanization. Specifically, areas with large changes were concentrated in urban core areas and economic development zones. (2) The matching degree between ESs supply and demand is quite diverse and shows a trend of polarization. Under the influence of urbanization, some cities began facing ESs supply shortages. (3) Overall, the CCD between ESs supply and demand in the study area is in a state of mild incoordination, but with increasing urbanization, some cities have turned into a state of extreme incoordination. Our results indicate that the ESs supply and demand status in some cities at the urban agglomeration scale has become increasingly severe. Therefore, it is necessary to focus on certain "key areas" to formulate optimization strategies. For key areas with "low supply-high demand" and extreme incoordination, the population and land use intensity should be controlled to reduce the ESs demand level. Meanwhile, for key areas with "high supply-low demand" and extreme incoordination, the utilization efficiency of ecological resources should be improved to enhance the ESs supply capacity. The results of this study will help decision-makers optimize the relationship between ESs supply and demand in order to achieve the sustainable development of urban agglomeration.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148173DOI Listing
June 2021

Histone modifications and chromatin remodelling in plants in response to salt stress.

Physiol Plant 2021 May 24. Epub 2021 May 24.

School of Life Sciences and Centre for Soybean Research of the State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Shatin, Hong Kong, China.

In the face of global food security crises, it is necessary to boost agricultural production. One factor hampering the attempts to increase food production is elevated soil salinity, which can be due to salt that is naturally present in the soil or a consequence of excessive or prolonged irrigation or application of fertiliser. In response to environmental stresses, plants activate multiple molecular mechanisms, including the timely activation of stress-responsive transcriptional networks. However, in the case of salt stress, the combined effects of the initial osmotic shock and the subsequent ion-specific stress increase the complexity in the selective regulation of gene expressions involved in restoring or maintaining osmotic balance, ion homeostasis and reactive oxygen species scavenging. Histone modifications and chromatin remodelling are important epigenetic processes that regulate gene expressions by modifying the chromatin status and recruiting transcription regulators. In this review, we have specifically summarised the currently available knowledge on histone modifications and chromatin remodelling in relation to plant responses to salt stress. Current findings have revealed the functional importance of chromatin modifiers in regulating salt tolerance and identified the effector genes affected by epigenetic modifications, although counteraction between modifiers within the same family may occur. Emerging evidence has also illustrated the crosstalk between epigenetic modifications and hormone signalling pathways which involves formation of protein complexes. With an improved understanding of these processes, plant breeders will be able to develop alternative strategies using genome editing technologies for crop improvement.
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http://dx.doi.org/10.1111/ppl.13467DOI Listing
May 2021

Blind placement of postpyloric feeding tubes at the bedside in intensive care.

Crit Care 2021 05 11;25(1):168. Epub 2021 May 11.

Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University, 253 Gongye Middle Avenue, Haizhu District, Guangzhou, 510280, Guangdong, China.

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http://dx.doi.org/10.1186/s13054-021-03587-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111987PMC
May 2021

CAG RNAs induce DNA damage and apoptosis by silencing expression in polyglutamine degeneration.

Proc Natl Acad Sci U S A 2021 May;118(19)

Laboratory of Drosophila Research, The Chinese University of Hong Kong, Hong Kong, China;

DNA damage plays a central role in the cellular pathogenesis of polyglutamine (polyQ) diseases, including Huntington's disease (HD). In this study, we showed that the expression of untranslatable expanded CAG RNA per se induced the cellular DNA damage response pathway. By means of RNA sequencing (RNA-seq), we found that expression of the () gene was down-regulated in mutant CAG RNA-expressing cells. The loss of NUDT16 function results in a misincorporation of damaging nucleotides into DNAs and leads to DNA damage. We showed that small CAG (sCAG) RNAs, species generated from expanded CAG transcripts, hybridize with CUG-containing mRNA and form a CAG-CUG RNA heteroduplex, resulting in gene silencing of and leading to the DNA damage and cellular apoptosis. These results were further validated using expanded CAG RNA-expressing mouse primary neurons and in vivo R6/2 HD transgenic mice. Moreover, we identified a bisamidinium compound, DB213, that interacts specifically with the major groove of the CAG RNA homoduplex and disfavors the CAG-CUG heteroduplex formation. This action subsequently mitigated RNA-induced silencing complex (RISC)-dependent silencing in both in vitro cell and in vivo mouse disease models. After DB213 treatment, DNA damage, apoptosis, and locomotor defects were rescued in HD mice. This work establishes NUDT16 deficiency by CAG repeat RNAs as a pathogenic mechanism of polyQ diseases and as a potential therapeutic direction for HD and other polyQ diseases.
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http://dx.doi.org/10.1073/pnas.2022940118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126783PMC
May 2021

Systematic analysis of JmjC gene family and stress--response expression of KDM5 subfamily genes in .

PeerJ 2021 31;9:e11137. Epub 2021 Mar 31.

Key Laboratory of Crop Epigenetic Regulation and Development, Hunan Province, Changsha, China.

Background: Jumonji C (JmjC) proteins exert critical roles in plant development and stress response through the removal of lysine methylation from histones. which originated from spontaneous hybridization by and , is the most important oilseed crop after soybean. In JmjC proteins of species, the structure and function and its relationship with the parents and model plant remain uncharacterized. Systematic identification and analysis for JmjC family in crops can facilitate the future functional characterization and oilseed crops improvement.

Methods: Basing on the conserved JmjC domain, JmjC homologs from the three species, (AA), (CC) and were identified from the database. Some methods, such as phylogenic analysis, chromosomal mapping, HMMER searching, gene structure display and Logos analysis, were used to characterize relationships of the JmjC homologs. Synonymous and nonsynonymous nucleotide substitutions were used to infer the information of gene duplication among homologs. Then, the expression levels of subfamily genes were checked under abiotic stress by qRT-PCR.

Results: Sixty-five JmjC genes were identified from genome, 29 from and 23 from . These genes were grouped into seven clades based on the phylogenetic analysis, and their catalytic activities of demethylation were predicted. The average retention rate of genes ( gene from (93.1%) and (82.6%)) exceeded whole genome level. JmjC sequences demonstrated high conservation in domain origination, chromosomal location, intron/exon number and catalytic sites. The gene duplication events were confirmed among the homologs. Many of the subfamily genes showed higher expression under drought and NaCl treatments, but only a few genes were involved in high temperature stress.

Conclusions: This study provides the first genome-wide characterization of JmjC genes in species. The exhibits higher conservation during the formation process of allotetraploid than the average retention rates of the whole genome. Furthermore, expression profiles of many genes indicated that subfamily genes are involved in stress response to salt, drought and high temperature.
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http://dx.doi.org/10.7717/peerj.11137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019318PMC
March 2021

Genetic polymorphisms in lncRNAs predict recurrence of ischemic stroke.

Metab Brain Dis 2021 Aug 5;36(6):1353-1359. Epub 2021 Apr 5.

Department of Neurology, First Affiliated Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang, 110001, Liaoning, China.

Genetic polymorphisms in long non-coding RNAs (lncRNAs) are considered as potential genetic biomarkers for the prediction of human complex diseases such as ischemic stroke (IS). However, so far, no reports have focused on the relationship of lncRNA polymorphisms with IS onset and prognosis. In our study, eight potential functional polymorphisms of four well-known lncRNAs (H19 rs2107425 and rs2251375, MALAT1 rs4102217 and rs3200401, MEG3 rs11160608 and rs4081134, SENCR rs4526784 and rs555172) were genotyped in 657 ischemic stroke patients. Then, the association between lncRNA polymorphisms and IS onset and recurrence were investigated. These lncRNA variants were not associated with age onset of IS. However, we observed that MEG3 rs4081134 AA genotype was statistically related with a reduced risk of stroke recurrence, particularly for patients with large-artery atherosclerotic stroke. Also, the decreased risk was more prominent in elders, non-smokers, non-drinkers and hypertensive patients. Furthermore, the variant genotype AA of rs4081134 was an independent predictor for IS recurrence using the multivariate Cox regression model. Our findings indicated that MEG3 rs4081134 can serve as a useful biomarker and potential therapeutic target in IS recurrence. More researches are needed to verify our results and explore the underlying molecular mechanisms.
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http://dx.doi.org/10.1007/s11011-021-00725-4DOI Listing
August 2021

Association Between Genetic Variants in the lncRNA-p53 Regulatory Network and Ischemic Stroke Prognosis.

Neurotox Res 2021 Aug 2;39(4):1171-1180. Epub 2021 Apr 2.

Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.

Long noncoding RNAs (lncRNAs) serve as regulators or effectors of the p53 regulatory pathway. The lncRNA-p53 regulatory network plays an important role in ischemia-induced apoptosis and may be important for post-stroke recovery. Eight genetic variants of p53-related lncRNAs were genotyped in 982 patients to explore the association of single nucleotide polymorphisms (SNPs) in the genes related to the p53 regulatory pathway with ischemic stroke (IS) prognosis in a northern Chinese population. Long- and short-term outcomes were assessed by stroke recurrence and modified Rankin Scale score 3 months after stroke, respectively. We first identified that p53 rs1042522 and LINC-ROR rs2027701 could be associated with IS recurrence risk. On further cumulative effect analysis, we found that these two polymorphisms could jointly be associated with IS recurrence. Patients carrying 2-4 risk alleles showed a significantly higher IS recurrence risk than those harboring no or a single risk allele. In contrast to rs2027701 and rs1042522, the other SNPs were not associated with IS recurrence. Subsequently, we found that TUG1 rs2240183 CC genotype was associated with a favorable IS outcome after adjusting for confounding factors. However, the other seven genetic variants of p53-related lncRNAs were not associated with a functional outcome after stroke. p53 rs1042522 and LINC-ROR rs2027701 may exert combined effects on IS recurrence, and TUG1 rs2240183 may be a new biomarker to predict short-term IS outcomes as it modulates p53-mediated apoptosis.
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http://dx.doi.org/10.1007/s12640-021-00357-7DOI Listing
August 2021

Effect of tap dance on plantar pressure, postural stability and lower body function in older patients at risk of diabetic foot: a randomized controlled trial.

BMJ Open Diabetes Res Care 2021 03;9(1)

Xigang Community Health Service Center, Nanjing, China.

Introduction: To examine the effects of tap dance (TD) on dynamic plantar pressure, static postural stability, ankle range of motion (ROM), and lower extremity functional strength in patients at risk of diabetic foot (DF).

Research Design And Methods: A randomised, single-blinded, two-arm prospective study of 40 patients at risk of DF was conducted. The intervention group (n=20) received 16 weeks of TD training (60 min/session×3 sessions/week). The control group attended four educational workshops (1 hour/session×1 session/month). Plantar pressure, represented by the primary outcomes of peak pressure (PP) and pressure-time integral (PTI) over 10 areas on each foot, was measured using the Footscan platform system. Secondary outcomes comprised static postural stability, ankle ROM and lower extremity functional strength.

Results: Reductions in intervention group PP (right foot: mean differences=4.50~27.1, decrease%=25.6~72.0; left foot: mean differences=-5.90~6.33, decrease%=-22.6~53.2) and PTI at 10 areas of each foot (right foot: mean differences=1.00~12.5, decrease%=10.4~63.6; left foot: mean differences=0.590~25.3, decrease%=21.9~72.6) were observed. Substantial PP and PTI differences were noted at the second through fourth metatarsals, medial heel and lateral heel in the right foot. Substantial PP and PTI differences were detected at metatarsals 1 and 2 and metatarsal 2 in the left foot, respectively. Moderate training effects were found in plantar flexion ROM of both feet, lower extremity functional strength, and length of center-of-pressure trajectory with eyes closed and open (=0.321-0.376, p<0.05).

Conclusions: A 16-week TD training program can significantly improve ankle ROM, lower extremity functional strength, and static postural stability. To attain greater improvements in plantar pressure, a longer training period is necessary.

Trial Registration Number: ChiCTR1800014714.
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http://dx.doi.org/10.1136/bmjdrc-2020-001909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978263PMC
March 2021

Association between lncRNA ANRIL genetic variants with the susceptibility to ischemic stroke: From a case-control study to meta-analysis.

Medicine (Baltimore) 2021 Mar;100(11):e25113

Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, China.

Background: Recent studies have reported that lncRNA (long noncoding RNAs) antisense non-coding RNA in the INK4 locus (ANRIL) plays important roles in the development of atherosclerosis through regulating cell apoptosis, proliferation, and adhesion. GWAS (genome-wide association studies) identified common genetic variants within ANRIL could confer risk of ischemic stroke (IS) in southern Sweden.

Methods: We performed a case-control study, including 567 IS patients and 552 healthy controls from unrelated northern Chinese Han population, aiming to explore the association between lncRNA ANRIL rs2383207, rs4977574 polymorphisms and the risk of IS. Subsequently we implemented a meta-analysis to further assess the relationship of these variants and the disease.

Results: In our case-control study, no significant associations were observed in all models between above 2 polymorphisms and IS. Next in our subgroup analysis, we detected significant association between GA genotype of rs4977574 and the increased risk of LAA-IS (large-artery atherosclerotic ischemic stroke), similar elevated risk also appeared in the GG + GA genotype under the dominant model (P = .048, OR = 1.385, 95% CIs 1.002-1.914; P = .040, OR = 1.378, 95% CIs 1.015-1.872, respectively). As for rs2383207, negative results were obtained under all models and subgroups. Our meta-analysis showed a significant association between rs4977574 polymorphism and IS risk in allele model (G vs A P = .002, OR = 1.137, 95% CIs 1.048-1.234); with respect to rs2383207 polymorphism, no significant association between that and the risk of IS was detected under the dominant model (GA + AA vs GG, P = .061, OR = 0.923, 95% CIs 0.849-1.004), or recessive model (AA vs GA + GG, P = .656, OR = 0.972, 95% CIs 0.858-1.101), or allele model (A vs G, P = .326, OR = 0.952, 95% CIs 0.863-1.050). Likewise, no significant association between rs2383207 and IS was found in different stoke subtypes (P > .05).

Conclusions: Our findings indicated G allele of lncRNA ANRIL rs4977574 could increase the risk of IS, and the variant may be associated with susceptibility to LAA-IS in Chinese Han population.
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http://dx.doi.org/10.1097/MD.0000000000025113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982178PMC
March 2021

Transcriptome Analysis Reveals the Genes Involved in FGSZY16M3 Biofilm Formation.

Microorganisms 2021 Feb 14;9(2). Epub 2021 Feb 14.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

Biofilm formation has evolved as an adaptive strategy for bacteria to cope with harsh environmental conditions. Currently, little is known about the molecular mechanisms of biofilm formation in bifidobacteria. A time series transcriptome sequencing analysis of both biofilm and planktonic cells of FGSZY16M3 was performed to identify candidate genes involved in biofilm formation. Protein-protein interaction network analysis of 1296 differentially expressed genes during biofilm formation yielded 15 clusters of highly interconnected nodes, indicating that genes related to the SOS response (, , , , , , and ) associated with the early stage of biofilm formation. Genes involved in extracellular polymeric substances were upregulated (, , , , , , , , and ) in the stage of biofilm maturation. To further investigate the genes related to biofilm formation, weighted gene co-expression network analysis (WGCNA) was performed with 2032 transcript genes, leading to the identification of nine WGCNA modules and 133 genes associated with response to stress, regulation of gene expression, quorum sensing, and two-component system. These results indicate that biofilm formation in is a multifactorial process, involving stress response, structural development, and regulatory processes.
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http://dx.doi.org/10.3390/microorganisms9020385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917626PMC
February 2021

Hydroxylation, Epoxidation, and Dehydrogenation of Capsaicin by a Microbial Promiscuous Cytochrome P450 105D7.

Chem Biodivers 2021 Apr 3;18(4):e2000910. Epub 2021 Mar 3.

College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, 310018, P. R. China.

Cytochrome P450 enzymes (P450s) are versatile biocatalysts, which insert a molecular oxygen into inactivated C-H bonds under mild conditions. CYP105D7 from Streptomyces avermitilis has been reported as a bacterial substrate-promiscuous P450 which catalyzes the hydroxylation of 1-deoxypentalenic acid, diclofenac, naringenin, compactin and steroids. In this study, CYP105D7 catalyzes hydroxylation, epoxidation and dehydrogenation of capsaicin, a pharmaceutical agent, revealing its functional diversity. The kinetic parameters of the CYP105D7 oxidation of capsaicin were determined as K =311.60±87.30 μM and k =2.01±0.33 min . In addition, we conducted molecular docking, mutagenesis and substrate binding analysis, indicating that Arg81 plays crucial role in the capsaicin binding and catalysis. To our best knowledge, this study presents the first report to illustrate that capsaicin can be catalyzed by prokaryotic P450s.
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http://dx.doi.org/10.1002/cbdv.202000910DOI Listing
April 2021

Enhanced anti-amnestic effect of donepezil by Ginkgo biloba extract (EGb 761) via further improvement in pro-cholinergic and antioxidative activities.

J Ethnopharmacol 2021 Apr 25;269:113711. Epub 2020 Dec 25.

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, People's Republic of China; Institute of Integrated Chinese and Western Medicine, Fudan University, Shanghai, 200040, People's Republic of China. Electronic address:

Ethnopharmacological Relevance: EGb 761 is a standardized dry extract of Ginkgo biloba L. leaves traditionally used by Eastern Asia and has been associated with beneficial effects on neurodegeneration disorders, including Alzheimer's disease.

Aim Of The Study: Since beneficial interactions between EGb 761 and donepezil have been observed in previous clinical studies, the current study was proposed aiming to further explore related mechanisms from both pharmacokinetics and pharmacodynamics aspects.

Materials And Methods: Pharmacodynamic interactions were studied in scopolamine-induced cognitive impairment rats received two-weeks treatment of vehicle, EGb 761 and/or donepezil by the Morris water maze test and ex vivo evaluation of biomarkers of cholinergic transmission and oxidative stress in rat brain. In the meantime, pharmacokinetic profiles of donepezil and bilobalide were obtained and compared among all treatment groups. In addition, impact of the bioavailable EGb 761 components on donepezil brain penetration was evaluated with the hCMEC/D3 cell monolayer model.

Results: Scopolamine-induced rats with co-treatment of EGb 761 and donepezil had significantly improved cognitive function in the Morris water maze test with increased brain levels of superoxide dismutase and decreased brain levels of acetylcholinesterase and malondialdehyde than that with treatment of only EGb 761 or donepezil. Despite such beneficial pharmacodynamics outcomes, the two-week co-treatment of EGb 761 and donepezil did not alter the plasma pharmacokinetics and brain uptake of donepezil or bilobalide, which was further verified in the hCMEC/D3 monolayer model.

Conclusion: Co-administration of EGb 761 and donepezil exerted better anti-amnestic effect via further enhanced pro-cholinergic and antioxidative effects of EGb 761 or donepezil in scopolamine-induced cognitive impairment rat without alteration in their systemic/brain exposure.
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http://dx.doi.org/10.1016/j.jep.2020.113711DOI Listing
April 2021

An expedient survey and characterization of the soybean JAGGED 1 (GmJAG1) transcription factor binding preference in the soybean genome by modified ChIPmentation on soybean protoplasts.

Genomics 2021 Jan 15;113(1 Pt 1):344-355. Epub 2020 Dec 15.

School of Life Sciences and Center for Soybean Research of the State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, PR China. Electronic address:

ChIP-seq is widely used for mapping the transcription factor (TF) binding sites throughout the genome in vivo. In this study, we adopted and modified ChIPmentation, a fast, robust, low-input requirement ChIP-seq method, to a transient expression system using soybean protoplasts to expedite the exploration of TF binding sites. To test this new protocol, we expressed a tagged version of a C2H2-type zinc finger TF, JAGGED1 (GmJAG1), in soybean protoplasts and successfully identified its binding sites in the soybean genome. Furthermore, valuable genomic features such as a novel GmJAG1-binding motif, and the epigenetic characteristics as well as an enhancer-like function of GmJBSs were also found via coupling ATAC-seq and H3K27me3 ChIP-seq data. The application of the modified ChIPmentation protocol in this study using soybean protoplasts provided a new approach for rapid elucidation of how a TF binds to the various target genes in the soybean genome, as illustrated here using GmJAG1.
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http://dx.doi.org/10.1016/j.ygeno.2020.12.026DOI Listing
January 2021

Abscisic Acid Is Required for Root Elongation Associated With Ca Influx in Response to Water Stress.

Front Plant Sci 2020 22;11:332. Epub 2020 Apr 22.

Center for Plant Water-Use and Nutrition Regulation and College of Resources and Environment, Joint International Research Laboratory of Water and Nutrient in Crops and College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.

Abscisic acid (ABA) is a critical hormone for plant survival under water stress. In this study, large-scale mutants of the ecotype Columbia-0 (Col-0) were generated by ethyl methanesulfonate (EMS)-mutagenesis, and an mutant showing significantly enhanced root growth was isolated under a water potential gradient assay. Then, and ABA-related mutants in or tomato plants were observed under water potential gradient assay or water-deficient conditions. ABA pathway, Ca response, and primary root (PR) elongation rate were monitored in addition to DNA- and RNA-Seq analyses. We found that based on phenotyping and transcriptional analyses, exhibited enhanced PR growth, ABA, and Ca responses, compared to wild type subjected to water stress. Interestingly, exogenous Ca application enhanced PR growth of , ABA-biosynthesis deficient mutants in , and tomato plants, in response to water potential gradients or water-deficient conditions. In combination with other ABA-related mutants and pharmacological studies, our results suggest that ABA is required for root elongation associated with Ca influx in response to water stress.
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http://dx.doi.org/10.3389/fpls.2020.00332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188952PMC
April 2020

A modified crescent cartilage block for improving the retroauricular contour of the reconstructed ear: A retrospective cohort study.

J Plast Reconstr Aesthet Surg 2021 06 1;74(6):1324-1330. Epub 2020 Nov 1.

Face and Neck Aesthetic and Plastic Surgery Center, Chinese Academy of Medical Sciences and Peking Union Medical College, 33 Badachu Road, Shijingshan District, Beijing 100144, China. Electronic address:

Background: The use of a semilunar cartilage block to elevate a reconstructed ear does not always achieve a well-defined auriculocephalic sulcus. Herein, we modified the conventional crescent cartilage block through sculpting a concavity at its posterior surface, with the aim of improving the retroauricular contour. The study aimed to verify the effectiveness and reliability of this modified cartilage block through a retrospective cohort study.

Methods: A retrospective review of patients who underwent Nagata microtia reconstruction between October 2017 and November 2018 were conducted. The esthetic outcomes of auricular projection and cranioauricular sulcus in patients who accepted the modified semilunar block were compared with those of patients who underwent the same procedure using the traditional crescent pad.

Results: A total of 163 (84 of the modified group and 79 of the traditional group) patients were included. The mean (median) esthetic scores for ear projection in the modification and traditional groups were 3.13 (3) and 3.06 (3), respectively. The rate of favorable ear projection in the modification group (83.3%) was similar with that in the traditional group (78.5%) (p = 0.550). The mean (median) esthetic scores for cranioauricular sulcus in the modification and traditional groups were 2.51 (3) and 2.90 (3), respectively. The rate of favorable retroauricular sulcus in the modification group was 75.9%, whereas that in the traditional group was 51.2%, with the differences reaching statistical significance (p = 0.001).

Conclusions: The concave crescent-shaped block can improve the contour of the auriculocephalic sulcus under the premise of ensuring the ear projection.
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http://dx.doi.org/10.1016/j.bjps.2020.10.021DOI Listing
June 2021

Visual Analysis of Discrimination in Machine Learning.

IEEE Trans Vis Comput Graph 2021 Feb 28;27(2):1470-1480. Epub 2021 Jan 28.

The growing use of automated decision-making in critical applications, such as crime prediction and college admission, has raised questions about fairness in machine learning. How can we decide whether different treatments are reasonable or discriminatory? In this paper, we investigate discrimination in machine learning from a visual analytics perspective and propose an interactive visualization tool, DiscriLens, to support a more comprehensive analysis. To reveal detailed information on algorithmic discrimination, DiscriLens identifies a collection of potentially discriminatory itemsets based on causal modeling and classification rules mining. By combining an extended Euler diagram with a matrix-based visualization, we develop a novel set visualization to facilitate the exploration and interpretation of discriminatory itemsets. A user study shows that users can interpret the visually encoded information in DiscriLens quickly and accurately. Use cases demonstrate that DiscriLens provides informative guidance in understanding and reducing algorithmic discrimination.
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http://dx.doi.org/10.1109/TVCG.2020.3030471DOI Listing
February 2021

HypoML: Visual Analysis for Hypothesis-based Evaluation of Machine Learning Models.

IEEE Trans Vis Comput Graph 2021 Feb 28;27(2):1417-1426. Epub 2021 Jan 28.

In this paper, we present a visual analytics tool for enabling hypothesis-based evaluation of machine learning (ML) models. We describe a novel ML-testing framework that combines the traditional statistical hypothesis testing (commonly used in empirical research) with logical reasoning about the conclusions of multiple hypotheses. The framework defines a controlled configuration for testing a number of hypotheses as to whether and how some extra information about a "concept" or "feature" may benefit or hinder an ML model. Because reasoning multiple hypotheses is not always straightforward, we provide HypoML as a visual analysis tool, with which, the multi-thread testing results are first transformed to analytical results using statistical and logical inferences, and then to a visual representation for rapid observation of the conclusions and the logical flow between the testing results and hypotheses. We have applied HypoML to a number of hypothesized concepts, demonstrating the intuitive and explainable nature of the visual analysis.
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http://dx.doi.org/10.1109/TVCG.2020.3030449DOI Listing
February 2021

SineStream: Improving the Readability of Streamgraphs by Minimizing Sine Illusion Effects.

IEEE Trans Vis Comput Graph 2021 Feb 28;27(2):1634-1643. Epub 2021 Jan 28.

In this paper, we propose SineStream, a new variant of streamgraphs that improves their readability by minimizing sine illusion effects. Such effects reflect the tendency of humans to take the orthogonal rather than the vertical distance between two curves as their distance. In SineStream, we connect the readability of streamgraphs with minimizing sine illusions and by doing so provide a perceptual foundation for their design. As the geometry of a streamgraph is controlled by its baseline (the bottom-most curve) and the ordering of the layers, we re-interpret baseline computation and layer ordering algorithms in terms of reducing sine illusion effects. For baseline computation, we improve previous methods by introducing a Gaussian weight to penalize layers with large thickness changes. For layer ordering, three design requirements are proposed and implemented through a hierarchical clustering algorithm. Quantitative experiments and user studies demonstrate that SineStream improves the readability and aesthetics of streamgraphs compared to state-of-the-art methods.
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http://dx.doi.org/10.1109/TVCG.2020.3030404DOI Listing
February 2021

The histone modification H3K4me3 marks functional genes in soybean nodules.

Genomics 2020 11 26;112(6):5282-5294. Epub 2020 Sep 26.

Center for Soybean Research of the State Key Laboratory of Agrobiotechnology and School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China. Electronic address:

Nitrogen fixation in legumes requires the development of specialized organs called root nodules. Here we characterized the high-confidence transcriptome and genome-wide patterns of H3K4me3 marks in soybean roots and mature nodules symbiotic with Sinorhizobium fredii. Changes in H3K4me3 levels were positively associated with the transcription levels of functional genes in the nodules. The up-regulation of H3K4me3 levels was not only present in leghaemoglobin and nodulin-related genes, but also in genes involved in nitrogen and carbon metabolic pathways. In addition, genes regulating the transmembrane transport of metal ions, phosphates, sulphates, peptides, and sugars were differentially modified. On the contrary, a loss of H3K4me3 marks was found in several key transcription factor genes and was correlated with the down-regulation of the defense-related network in nodules, which could contribute to nodule maintenance. All these findings demonstrate massive reprogramming of gene expressions via alterations in H3K4me3 levels in the genes in mature soybean nodules.
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http://dx.doi.org/10.1016/j.ygeno.2020.09.052DOI Listing
November 2020

Circular RNAs: novel diagnostic and therapeutic targets for ischemic stroke.

Expert Rev Mol Diagn 2020 10 5;20(10):1039-1049. Epub 2020 Oct 5.

Department of Neurology, The First Affiliated Hospital of China Medical University , Shenyang, China.

Introduction: Ischemic stroke is a life-threatening condition worldwide, including China. Nowadays, intravenous thrombolysis and mechanical thrombectomy are chiefly applied as clinical therapeutics; however, strict time windows and underlying risks limit their benefits for patients. Thus, it is urgently needed to seek new effective targets for stroke to improve clinical outcomes.

Areas Covered: Circular RNAs have recently emerged as ideal therapeutic candidates for ischemic stroke with high stability and evolutionary conservation in the brain tissue. The neurovascular unit is a microscopic and complex three-dimensional domain key in the processes of this disease, and reflects diverse structures and functions of the brain tissue. During the progression of ischemic stroke, circular RNAs are extensively involved in the responses of the neurovascular unit including atherosclerosis, neuroinflammation, apoptosis, and neurogenesis. Additionally, they display diagnostic, monitoring, therapeutic, and prognostic effects in the occurrence of and recovery from the disease.

Expert Opinion: Exploration of circular RNAs and their correlated effects in ischemic stroke may facilitate accurate diagnosis and serve as new therapeutic targets for the disease.
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http://dx.doi.org/10.1080/14737159.2020.1826313DOI Listing
October 2020

Cross-cultural modifications and measurement properties of the CHAMPS questionnaire among Chinese older adults.

J Exerc Sci Fit 2021 Jan 28;19(1):13-18. Epub 2020 Jul 28.

Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210046, China.

Background/objective: The Community Health Activities Model Program for Seniors questionnaires (CHAMPS-Q) is one of the most extensively used instruments in assessing physical activity among older adults. However, no study had translated the CHAMPS-Q into Chinese, and no evaluations were made on the psychometric properties of the CHAMPS-Q among the Chinese population. Considering cultural differences in perceptions of language, cultural context and living habits, this study was of necessary to 1) translate and cross-culturally adapt the original CHAMPS-Q, and 2) examine the test-retest reliability and construct/predictive validity of the Chinese version of the CHAMPS-Q.

Methods: The English CHAMPS-Q was first translated into Chinese, synthesized, back-translated, and revised by an expert committee according to the pre-test results. The Chinese CHAMPS-Q was then assessed in a cross-sectional study consisting of 101 apparently healthy older adults. Test-retest reliability test was conducted with 7 days apart. The construct validity of the Chinese CHAMPS-Q was tested against accelerometer data, and the predictive validity was assessed against physical fitness as measured by the Senior Fitness Test.

Results: The Chinese CHAMPS-Q has moderate to excellent test-retest reliability ( = 0.72-.96,  < .05). Energy expenditure and duration in PA significantly correlated with all accelerometry outcomes ( = 0.22-.31,  < .05). All the outcomes from the CHAMPS-Q showed significant correlations with upper body muscle strength ( = 0.22-.34,  < .05).

Conclusion: The Chinese CHAMPS-Q has excellent test-retest reliability and acceptable construct and predictive validity in assessing the physical activity of Chinese older adults.
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http://dx.doi.org/10.1016/j.jesf.2020.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452187PMC
January 2021

Association of GWAS-susceptibility loci with ischemic stroke recurrence in a Han Chinese population.

J Gene Med 2021 Jan 9;23(1):e3264. Epub 2020 Sep 9.

Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, China.

Background: Recently, genome-wide association studies (GWAS) have found many new susceptible genetic variants for ischemic stroke (IS) occurrence. However,the roles of GWAS-susceptibility loci in stroke prognosis are just beginning. The present study aimed to examine whether these GWAS-linked loci polymorphisms are associated with ischemic stroke recurrence in a Chinese population.

Methods: We genotyped six single nucleotide polymorphisms (SNPs) (9p21: rs2383207 and rs4977574; 12p13: rs12425791 and rs11833579; PDE4D: rs966221; and ALOX5AP: rs1050391) in four GWAS-reported ischemic stroke risk genes in 657 patients.

Results: The risk of recurrent stroke was significantly associated with PDE4D rs966221 in the dominant model (p = 0.027)and recessive model (p = 0.027). Furthermore, Kaplan-Meier analyses indicated no significant difference in the rate of recurrent stroke among the three genotypes of other five SNPs. Cox regression analysis showed that the GA + GG genotype within the rs966221 polymorphism had a 1.399-fold risk for stoke recurrence (95% confidence interval = 1.038-1.886; p = 0.027). Stratified analysis revealed that the increased recurrence risk of PDE4D rs966221 was more prominent in the large artery atherosclerosis (LAA) subgroup.

Conclusions: The reults of the present study demonstrate that PDE4D rs966221 may be a valuable biomarker for predicting the recurrent risks of patient with the LAA-IS and adds to our knowledge of the genetic basis of recurrent stroke risk.
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http://dx.doi.org/10.1002/jgm.3264DOI Listing
January 2021

Development of New Tuberculosis Drugs: Translation to Regimen Composition for Drug-Sensitive and Multidrug-Resistant Tuberculosis.

Annu Rev Pharmacol Toxicol 2021 01 17;61:495-516. Epub 2020 Aug 17.

Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California 94158, USA; email:

Tuberculosis (TB) kills more people than any other infectious disease. Challenges for developing better treatments include the complex pathology due to within-host immune dynamics, interpatient variability in disease severity and drug pharmacokinetics-pharmacodynamics (PK-PD), and the growing emergence of resistance. Model-informed drug development using quantitative and translational pharmacology has become increasingly recognized as a method capable of drug prioritization and regimen optimization to efficiently progress compounds through TB drug development phases. In this review, we examine translational models and tools, including plasma PK scaling, site-of-disease lesion PK, host-immune and bacteria interplay, combination PK-PD models of multidrug regimens, resistance formation, and integration of data across nonclinical and clinical phases.We propose a workflow that integrates these tools with computational platforms to identify drug combinations that have the potential to accelerate sterilization, reduce relapse rates, and limit the emergence of resistance.
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http://dx.doi.org/10.1146/annurev-pharmtox-030920-011143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790895PMC
January 2021

Release characteristics of mercury in chemical looping combustion of bituminous coal.

J Environ Sci (China) 2020 Aug 7;94:197-203. Epub 2020 May 7.

Engineering Laboratory of Energy System Process Conversion and Emission Reduction Technology of Jiangsu Province, School of Energy and Mechanical Engineering, Nanjing Normal University, Nanjing 210042, PR China.

This study evaluated the release characteristics of mercury from bituminous coal in chemical looping combustion (CLC) using Australian iron ore as the oxygen carrier in a fixed bed reactor. The effects of several parameters, such as temperature in the fuel reactor (FR) and air reactor (AR), gasification medium in the FR, and reaction atmosphere in the AR, on mercury release characteristics, were investigated. The mercury speciation and release amount in the FR and AR under different conditions were further explored. The results indicate that most of the mercury in coal was released in the FR, while the rest of it was released in the AR. Hg was found to be the major species in the released mercury. The results also indicate that a higher temperature in the FR led to an increase in the total mercury release amount and a decrease in Hg proportion. However, a higher temperature in the AR resulted in a decrease in the total mercury release amount and Hg proportion. The increase in the HO/CO ratio of gasification mediums in the FR was beneficial for the increase in the total mercury release amount and Hg proportion. A higher O concentration in reaction atmosphere in AR had a negligible effect on the total mercury release amount, but a positive effect on Hg oxidization.
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http://dx.doi.org/10.1016/j.jes.2020.03.017DOI Listing
August 2020
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