46 results on '"Zhou, Jingqi"'
Search Results
2. Associations of sex-related and thyroid-related hormones with risk of metabolic dysfunction-associated fatty liver disease in T2DM patients
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Lu, Weihong, Li, Shangjian, Li, Yuhua, Zhou, Jingqi, Wang, Kai, Chen, Ning, and Li, Zhibin
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- 2024
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3. Physical-layer secret key generation based on domain-adversarial training of autoencoder for spatial correlated channels
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Zhou, Jingqi and Zeng, Xin
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- 2023
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4. Draft Genome of White-blotched River Stingray Provides Novel Clues for Niche Adaptation and Skeleton Formation
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Zhou, Jingqi, Liu, Ake, He, Funan, Zhang, Yunbin, Shen, Libing, Yu, Jun, and Zhang, Xiang
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- 2023
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5. Oncogenic role of the SOX9-DHCR24-cholesterol biosynthesis axis in IGH-BCL2+ diffuse large B-cell lymphomas
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Shen, Yajie, Zhou, Jingqi, Nie, Kui, Cheng, Shuhua, Chen, Zhengming, Wang, Wenhan, Wei, Weiqing, Jiang, Daiji, Peng, Zijing, Ren, Yizhuo, Zhang, Yirong, Fan, Qiuju, Richards, Kristy L., Qi, Yitao, Cheng, Jinke, Tam, Wayne, and Ma, Jiao
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- 2022
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6. Cognitive disorders associated with hospitalization of COVID-19: Results from an observational cohort study
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Zhou, Jingqi, Liu, Chang, Sun, Yitang, Huang, Weishan, and Ye, Kaixiong
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- 2021
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7. Carbohydrate polymers exhibit great potential as effective elicitors in organic agriculture: A review
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Zheng, Fang, Chen, Lei, Zhang, Peifeng, Zhou, Jingqi, Lu, Xiaofang, and Tian, Wei
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- 2020
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8. Extensive Mendelian randomization study identifies potential causal risk factors for severe COVID-19
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Sun, Yitang, Zhou, Jingqi, and Ye, Kaixiong
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- 2021
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9. Anciently duplicated genes continuously recruited to heart expression in vertebrate evolution are associated with heart chamber increase.
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Zou, Yangyun, Yang, Jingwen, Zhou, Jingqi, Liu, Gangbiao, Shen, Libing, Zhou, Zhan, Su, Zhixi, and Gu, Xun
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HEART ,MAMMAL evolution ,MYOCARDIUM ,SEA squirts ,GENES ,VERTEBRATES ,ENERGY function - Abstract
Although gene/genome duplications in the early stage of vertebrates have been thought to provide major resources of raw genetic materials for evolutionary innovations, it is unclear whether they continuously contribute to the evolution of morphological complexity during the course of vertebrate evolution, such as the evolution from two heart chambers (fishes) to four heart chambers (mammals and birds). We addressed this issue by our heart RNA‐Seq experiments combined with published data, using 13 vertebrates and one invertebrate (sea squirt, as an outgroup). Our evolutionary transcriptome analysis showed that number of ancient paralogous genes expressed in heart tends to increase with the increase of heart chamber number along the vertebrate phylogeny, in spite that most of them were duplicated at the time near to the origin of vertebrates or even more ancient. Moreover, those paralogs expressed in heart exert considerably different functions from heart‐expressed singletons: the former are functionally enriched in cardiac muscle and muscle contraction‐related categories, whereas the latter play more basic functions of energy generation like aerobic respiration. These findings together support the notion that recruiting anciently paralogous genes that are expressed in heart is associated with the increase of chamber number in vertebrate evolution. Research Highlights: Correlation between the expression of paralogous genes and heart chamber complexity.Paralogs expressed in heart exert considerably different functions from heart‐expressed singletons.Paralogous genes expressed in heart is associated with the increase of chamber number in evolution. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Plumeriapropionics A–E, Carboxyl-Substituted Phenylpropionic Acid Derivatives with Anti-Inflammatory Activity from Plumeria rubra L.
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Zhou, Xueming, Gan, Minlin, Wu, Meizhu, Zheng, Ting, Enkhchimeg, Chuluunbaatar, Li, Haixiang, Feng, Shuo, Zhou, Jingqi, and Song, Xinming
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ACID derivatives ,ANTI-inflammatory agents ,NITRIC oxide ,LIPOPOLYSACCHARIDES - Abstract
Five rare carboxyl-substituted phenylpropionic acid derivatives, plumeriapropionics A–E (1–5), together with one known analog, cerberic acid B (6), were isolated from flowers of Plumeria rubra L. Their structures were elucidated using comprehensive spectroscopic methods. To date, only one compound of this structural type has been reported. The inhibitory activities of compounds 1–6 against nitric oxide (NO) production induced by lipopolysaccharide (LPS) were evaluated in vitro using mouse macrophage RAW264.7 cells. Compounds 1–6 showed remarkable inhibitory activities on NO production, with IC
50 values in the range of 6.52 ± 0.23 to 35.68 ± 0.17 µM. These results indicate that the discovery of carboxyl-substituted phenylpropionic acid derivatives from the flowers of P. rubra, which show significant anti-inflammatory properties, could be of great importance for the research and development of novel natural anti-inflammatory agents. [ABSTRACT FROM AUTHOR]- Published
- 2024
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11. Glycolytic enzyme Enolase-1 regulates insulin gene expression in pancreatic β-cell
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Luo, Xiumei, Luan, Cheng, Zhou, Jingqi, Ye, Yingying, Zhang, Wei, Jain, Ruchi, Zhang, Enming, and Chen, Ning
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- 2024
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12. Convergent degeneration of olfactory receptor gene repertoires in marine mammals
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Liu, Ake, He, Funan, Shen, Libing, Liu, Ruixiang, Wang, Zhijun, and Zhou, Jingqi
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- 2019
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13. Childhood obesity leads to adult type 2 diabetes and coronary artery diseases: A 2-sample mendelian randomization study
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Fang, Xuqian, Zuo, Junli, Zhou, Jingqi, Cai, Jialin, Chen, Changqiang, Xiang, Enfei, Li, Haibo, Cheng, Xiaoyan, and Chen, Peizhan
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- 2019
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14. Mutagenic Characteristics of Six Heavy Metals in Escherichia coli: The Commonality and Specificity.
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Ba, Qian, Zhou, Jingqi, Li, Jingquan, Cheng, Shujun, Zhang, Xiaokang, and Wang, Hui
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- 2023
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15. Association of Plasma Sex-Related Hormones Levels with Bone Mineral Densities and Risk of Osteoporosis and Osteopenia in Men and Menopausal Women with Type 2 Diabetes Mellitus.
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Lu, Weihong, Zheng, Silan, Zhou, Jingqi, Huang, Shunfa, Chen, Ning, and Li, Zhibin
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BONE density ,TYPE 2 diabetes ,OSTEOPENIA ,MENOPAUSE ,OSTEOPOROSIS ,DUAL-energy X-ray absorptiometry - Abstract
aimed to examine associations between plasma sex-related hormones with bone mineral density (BMD) and risks of osteoporosis or osteopenia in men and postmenopausal women patients with type 2 diabetes mellitus (T2DM). Methods: Baseline information on an ongoing cohort of 149 men and 102 postmenopausal women with T2DM in Xiamen, China were analyzed. Plasma estradiol (E2), total testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (PRL) were measured. BMD of lumbar spine (L2-4), femoral neck (FN) and total hip (TH) were determined by dual-energy X-ray absorptiometry (DXA). Osteoporosis or osteopenia was defined as the minimum T-scores of BMD of these three different sites of − 1.0 or below. Results: T2DM patients with osteoporosis/osteopenia (66.4% in men and 79.4% in postmenopausal women), compared to those without, showed significantly decreased level of E2 (75.3± 28.9 vs. 107.8± 25.9pmol/L and 18.4 (18.4– 29.5) vs. 22.8 (18.4– 40.5) pmol/L for men and postmenopausal women, respectively, both p-values < 0.05), but not other sex-related hormones (including T, FSH, LH, or PRL). For all T2DM patients together and men separately, multivariable linear regression and logistic regression analyses showed that higher E2 levels were significantly associated with higher BMD T-scores in L2-4, FN, TH and minimum of these three different sites, lower 10-year probability of major osteoporotic fractures (MOF) and hip fractures (HFs) estimated by Fracture Risk Assessment Tool score, as well as decreased risk of osteoporosis/osteopenia. As for postmenopausal women T2DM patients, E2 level was positively associated with BMD T-scores in L2-4 and minimum of three different sites but was not independently associated with risk of osteoporosis/osteopenia. Conclusion: Higher plasma E2 was significantly associated with increased BMD and lower risk of osteoporosis or osteopenia in T2DM patients, especially for men. Screening of BMD and estradiol levels as well as evaluating risks of osteoporosis/osteopenia are important for T2DM patients. [ABSTRACT FROM AUTHOR]
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- 2023
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16. Associations of Obesity Indices with Bone Mineral Densities and Risk of Osteoporosis Stratified Across Diabetic Vascular Disease in T2DM Patients.
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Zheng, Silan, Zhou, Jingqi, Wang, Kai, Wang, Xinyue, Li, Zhibin, and Chen, Ning
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DIABETIC angiopathies ,POSTMENOPAUSE ,DIABETIC retinopathy ,BONE density ,HYPERGLYCEMIA ,TYPE 2 diabetes ,OSTEOPOROSIS - Abstract
For those diabetes patients with any of diabetic vascular diseases, higher obesity indices, including body weight, BMI and waist, were significantly associated with lower minimum T-scores of BMD and decreased risk of osteoporosis. On the other hand, we were probably the first, to the best of our knowledge, to test the associations of obesity indices with BMD and osteoporosis stratified across presence of any diabetic vascular diseases and found various results between obesity indices and BMD for those with and without any diabetic vascular diseases. But for those patients without any of diabetic vascular diseases, none of the obesity indices was significantly associated with minimum T-scores of BMD, and results for obesity indices with osteoporosis could not be drawn since multivariable logistic regression models for these patients could not be converged. [Extracted from the article]
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- 2022
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17. Mutagenic Characteristics of Six Heavy Metals in Escherichia coli: The Commonality and Specificity.
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Ba, Qian, Zhou, Jingqi, Li, Jingquan, Cheng, Shujun, Zhang, Xiaokang, and Wang, Hui
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- 2022
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18. Application of Compound Polymyxin B Ointment in the Treatment of Chronic Refractory Wounds.
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Tang, Jiajun, Guan, Haonan, Dong, Wei, Liu, Yingkai, Dong, Jiaoyun, Huang, Lifang, Zhou, Jingqi, and Lu, Shuliang
- Abstract
The purpose of this study was to investigate the clinical efficacy of compound polymyxin B ointment for treating chronic refractory wounds. A retrospective analysis was performed on 111 patients who underwent chronic refractory wound treatment. Patients were divided into 2 groups, with 45 patients included in the experimental group (compound polymyxin B group) and 66 patients included in the control group (silver sulfadiazine group). After thorough debridement in both groups, either compound polymyxin B ointment or silver sulfadiazine cream was evenly applied to the patient's wound and covered with sterile gauze. In both groups, dressing changes were dependent on the wound's condition and secretions. Using the Bates-Jensen Wound Assessment Tool (BWAT), patients in both groups were scored, after which wound healing, infection, and healing time were compared. There was no significant difference in BWAT scores between the 2 groups on the 7th or 14th day; however, on the 21st day, the BWAT score in the experimental group was significantly lower than that of the control group. The difference was statistically significant (P <.05). There was no significant difference in the BWAT-I scores between the 2 groups on the seventh day. The healing time in the experimental group was significantly shorter than that of the control group, and the difference was statistically significant (P <.05). For the treatment of chronic refractory wounds, thorough debridement followed by compound polymyxin B ointment topical application can reduce and control wound infection effectively and accelerate the process of wound repair. [ABSTRACT FROM AUTHOR]
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- 2022
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19. Asymmetric Evolution of Human Transcription Factor Regulatory Networks
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Zhou, Zhan, Zhou, Jingqi, Su, Zhixi, and Gu, Xun
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- 2014
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20. Altered Blood Cell Traits Underlie a Major Genetic Locus of Severe COVID-19.
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Zhou, Jingqi, Sun, Yitang, Huang, Weishan, and Ye, Kaixiong
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COVID-19 , *BLOOD cells , *LEUCOCYTES , *BLOOD cell count , *OLDER people , *RESEARCH funding - Abstract
Background: The genetic locus 3p21.31 has been associated with severe coronavirus disease 2019 (COVID-19), but the underlying pathophysiological mechanism is unknown.Methods: To identify intermediate traits associated with the 3p21.31 locus, we first performed a phenome-wide association study (PheWAS) with 923 phenotypes in 310 999 European individuals from the UK Biobank. For genes potentially regulated by the COVID-19 risk variant, we examined associations between their expression and the polygenic score (PGS) of 1263 complex traits in a meta-analysis of 31 684 blood samples. For the prioritized blood cell traits, we tested their associations with age and sex in the same UK Biobank sample.Results: Our PheWAS highlighted multiple blood cell traits to be associated with the COVID-19 risk variant, including monocyte count and percentage (p = 1.07 × 10-8, 4.09 × 10-13), eosinophil count and percentage (p = 5.73 × 10-3, 2.20 × 10-3), and neutrophil percentage (p = 3.23 × 10-3). The PGS analysis revealed positive associations between the expression of candidate genes and genetically predicted counts of specific blood cells: CCR3 with eosinophil and basophil (p = 5.73 × 10-21, 5.08 × 10-19); CCR2 with monocytes (p = 2.40 × 10-10); and CCR1 with monocytes and neutrophil (p = 1.78 × 10-6, 7.17 × 10-5). Additionally, we found that almost all examined white blood cell traits are significantly different across age and sex groups.Conclusions: Our findings suggest that altered blood cell traits, especially those of monocyte, eosinophil, and neutrophil, may represent the mechanistic links between the genetic locus 3p21.31 and severe COVID-19. They may also underlie the increased risk of severe COVID-19 in older adults and men. [ABSTRACT FROM AUTHOR]- Published
- 2021
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21. Genome-wide association study of fish oil supplementation on lipid traits in 81,246 individuals reveals new gene-diet interaction loci.
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Francis, Michael, Li, Changwei, Sun, Yitang, Zhou, Jingqi, Li, Xiang, Brenna, J. Thomas, and Ye, Kaixiong
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FISH oils ,BLOOD lipids ,OMEGA-3 fatty acids ,LIPIDS ,FUNCTIONAL genomics ,GENES ,GENOME-wide association studies - Abstract
Fish oil supplementation is widely used for reducing serum triglycerides (TAGs) but has mixed effects on other circulating cardiovascular biomarkers. Many genetic polymorphisms have been associated with blood lipids, including high- and low-density-lipoprotein cholesterol (HDL-C, LDL-C), total cholesterol, and TAGs. Here, the gene-diet interaction effects of fish oil supplementation on these lipids were analyzed in a discovery cohort of up to 73,962 UK Biobank participants, using a 1-degree-of-freedom (1df) test for interaction effects and a 2-degrees-of-freedom (2df) test to jointly analyze interaction and main effects. Associations with P < 1×10
−6 in either test (26,157; 18,300 unique variants) were advanced to replication in up to 7,284 participants from the Atherosclerosis Risk in Communities (ARIC) Study. Replicated associations reaching 1df P < 0.05 (2,175; 1,763 unique variants) were used in meta-analyses. We found 13 replicated and 159 non-replicated (UK Biobank only) loci with significant 2df joint tests that were predominantly driven by main effects and have been previously reported. Four novel interaction loci were identified with 1df P < 5×10−8 in meta-analysis. The lead variant in the GJB6-GJB2-GJA3 gene cluster, rs112803755 (A>G; minor allele frequency = 0.041), shows exclusively interaction effects. The minor allele is significantly associated with decreased TAGs in individuals with fish oil supplementation, but with increased TAGs in those without supplementation. This locus is significantly associated with higher GJB2 expression of connexin 26 in adipose tissue; connexin activity is known to change upon exposure to omega-3 fatty acids. Significant interaction effects were also found in three other loci in the genes SLC12A3 (HDL-C), ABCA6 (LDL-C), and MLXIPL (LDL-C), but highly significant main effects are also present. Our study identifies novel gene-diet interaction effects for four genetic loci, whose effects on blood lipids are modified by fish oil supplementation. These findings highlight the need and possibility for personalized nutrition. Author summary: We utilized the unprecedentedly large genotype and phenotype dataset in the UK Biobank to perform a genome-wide association study (GWAS) which accounts for the interplay between genotype and dietary intake. We examined the interaction effects of fish oil supplementation on levels of blood lipids (LDL-C, HDL-C, TAGs, and total cholesterol). Our findings were replicated in the Atherosclerosis Risk in Communities (ARIC) Study. We found that at the genetic variant rs112803755 (A>G), the minor allele (G) is associated with a decrease in TAGs among individuals with fish oil supplementation, but is associated with an increase in TAGs among those without supplementation. In other words, only individuals carrying the minor allele benefit from fish oil supplementation in reducing TAG levels. We further analyzed rs112803755 with functional genomics data from the Genotype-Tissue Expression (GTEx) project to identify potential target genes, and found a connexin coding gene which has been previously reported to respond to cellular omega-3 levels. This research suggests that inter-personal variation in TAG response to fish oil supplementation is in part explained by genotype, and that fish oil dose adjustment based on genotype should be investigated as a means to protect against cardiovascular disease risk. [ABSTRACT FROM AUTHOR]- Published
- 2021
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22. Core-shell structured BaTiO3@SiO2 nanofibers for poly(vinylidene fluoride) nanocomposites with high discharged energy
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Liu, Shaohui, Wang, Jiao, Wang, Jingyi, Shen, Bo, Zhai, Jiwei, Guo, Chenguang, and Zhou, Jingqi
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- 2017
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23. Shared and Unique Clinical Effects of Five Circulating Minerals: A Comparative Phenome-Wide Mendelian-Randomization Study
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Zhou, Jingqi, Liu, Chang, Francis, Michael, Sun, Yitang, Ryu, Moon-Suhn, Grider, Arthur, and Ye, Kaixiong
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- 2021
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24. Genetic Variants Modifying the Triglycerides-Lowering Effect of Fish Oil Supplementation: A Genome-Wide Interaction Study
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Francis, Michael, Li, Changwei, Sun, Yitang, Zhou, Jingqi, Li, Xiang, Brenna, James, and Ye, Kaixiong
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- 2021
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25. SARS-CoV-2 Receptor ACE2 Is Enriched in a Subpopulation of Mouse Tongue Epithelial Cells in Nongustatory Papillae but Not in Taste Buds or Embryonic Oral Epithelium.
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Wang, Zhonghou, Zhou, Jingqi, Marshall, Brett, Rekaya, Romdhane, Ye, Kaixiong, and Liu, Hong-Xiang
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- 2020
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26. Epidemiological investigation of vascular etiological examinations in the diagnosis and treatment of lower‐extremity ulcers in China.
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Dong, Jiaoyun, Tian, Ming, Song, Fei, Tang, Jiajun, Liu, Yingkai, Wu, Minjie, Li, Jian, Zhou, Jingqi, Huang, Lifang, Dong, Wei, and Lu, Shuliang
- Subjects
BLOOD circulation ,VASCULAR diseases ,CHI-squared test ,DIAGNOSTIC errors ,EPIDEMIOLOGICAL research ,LEG ,LEG ulcers ,PHYSICAL diagnosis ,DESCRIPTIVE statistics ,DISEASE complications - Abstract
The vascular causes of lower‐extremity ulcers cannot be neglected because they can directly affect treatment methods. No detailed epidemiological statistics have described vascular etiological diagnosis in China. This study aimed to explore the prevalence of clinical vascular etiological examination of lower‐extremity ulcers and improve the diagnosis and treatment effectiveness of lower‐extremity ulcers. Data were collected from the WoundCareLog database, which includes 2413 cases of lower‐extremity ulcers from 478 hospitals nationwide. Data analysis revealed that 1698 (70.4%) lower‐extremity blood flow examinations (including physical examination [PE] and assistant examinations [AE]) were performed, of which 61.7% were PE, 10.4% were AE only, and 27.9% were the combined PE and AE[PAE]. The proportion of nonexaminations was higher in the nondiabetic group than in the diabetic group (χ2 = 34.5; P <.01). The positive rates of vascular etiological examination in the diabetic and nondiabetic groups were 69.7% and 70.7%, respectively. Among the four economic regions of China, there were statistically significant differences in the use of the different examination methods. The examination of vascular diseases in lower‐extremity ulcers in China has not been fully popularized and requires improvement; there was no statistically significant difference between examination rates by doctors and nurses, which is mainly based on PE. However, PE has certain rates of misdiagnosis and missed diagnosis. The false‐positive and false‐negative rates were 25.7% and 57.6%, respectively. The use of an AE can compensate for this deficiency by making diagnosis more precise, while the quantitative diagnostic criteria allow disease diagnosis to transcend geographical and operator differences and maximize uniformity. The vascular B‐ultrasound examination is more suitable for the medical environment in China because of its mature technology, high hospital penetration rate, and low cost. [ABSTRACT FROM AUTHOR]
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- 2020
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27. Genomic Survey of Tyrosine Kinases Repertoire in Electrophorus electricus With an Emphasis on Evolutionary Conservation and Diversification.
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Li, Ling, Liu, Dangyun, Liu, Ake, Li, Jingquan, Wang, Hui, and Zhou, Jingqi
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KINASES ,TYROSINE ,MOLECULAR evolution ,CELL growth - Abstract
Tyrosine kinases (TKs) play key roles in the regulation of multicellularity in organisms and involved primarily in cell growth, differentiation, and cell-to-cell communication. Genome-wide characterization of TKs has been conducted in many metazoans; however, systematic information regarding this superfamily in Electrophorus electricus (electric eel) is still lacking. In this study, we identified 114 TK genes in the E electricus genome and investigated their evolution, molecular features, and domain architecture using phylogenetic profiling to gain a better understanding of their similarities and specificity. Our results suggested that the electric eel TK (EeTK) repertoire was shaped by whole-genome duplications (WGDs) and tandem duplication events. Compared with other vertebrate TKs, gene members in Jak, Src, and EGFR subfamily duplicated specifically, but with members lost in Eph, Axl, and Ack subfamily in electric eel. We also conducted an exhaustive survey of TK genes in genomic databases, identifying 1674 TK proteins in 31 representative species covering all the main metazoan lineages. Extensive evolutionary analysis indicated that TK repertoire in vertebrates tended to be remarkably conserved, but the gene members in each subfamily were very variable. Comparative expression profile analysis showed that electric organ tissues and muscle shared a similar pattern with specific highly expressed TKs (ie, epha7, musk, jak1, and pdgfra), suggesting that regulation of TKs might play an important role in specifying an electric organ identity from its muscle precursor. We further identified TK genes exhibiting tissue-specific expression patterns, indicating that members in TKs participated in subfunctionalization representing an evolutionary divergence required for the performance of different tissues. This work generates valuable information for further gene function analysis and identifying candidate TK genes reflecting their unique tissue-function specializations in electric eel. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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28. Organocatalytic Asymmetric Michael Addition of Pyrazol-5-ones to β‑Trifluoromethyl-α,β-unsaturated Ketones: Stereocontrolled Construction of Vicinal Quaternary and Tertiary Stereocenters.
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Xu, Xinyao, He, Yanmin, Zhou, Jingqi, Li, Xinjuan, Zhu, Bo, and Chang, Junbiao
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- 2020
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29. prognostic signature of the somatic mutations in Ewing sarcoma: from a network view.
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Zhang, Yuehui, Song, Jia, Shi, Qili, Song, Xupu, Shen, Libing, Zhou, Jingqi, and Shao, Jiang
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- 2019
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30. The Motion of An Inv Nodal Cilium: a Realistic Model Revealing Dynein-Driven Ciliary Motion with Microtubule Mislocalization.
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Yu, Yanan, Xu, Huanming, Li, Zhenfeng, Xu, Yuanqing, Chen, Duanduan, Shinohara, Kyosuke, Nishida, Tomoki, Hamada, Hiroshi, Zhou, Jingqi, Shao, Daisy, and Li, Xiangchen
- Subjects
CILIA & ciliary motion ,DYNEIN ,THREE-dimensional modeling ,ELECTRON microscopy ,FINITE element method - Abstract
Background/Aims: Nodal cilia that rotate in the ventral node play an important role in establishing left-right asymmetry during embryogenesis; however, inv mutant cilia present abnormal movement and induce laterality defects. The mechanism of their motility, which is regulated by dynein activation and microtubule arrangement, has not been fully understood. This study analyzed the dynein-triggered ciliary motion in the abnormal ultrastructure of the inv mutant, aiming to quantitatively evaluate the influence of microtubule mislocalization on the movement of the cilium. Methods: We established a realistic 3-D model of an inv mutant cilium with an ultrastructure based on tomographic datasets generated by ultra-high voltage electron microscopy. The time-variant activation of the axonemal dynein force was simulated by pairs of point loads and embedded at dynein-mounted positions between adjacent microtubule doublets in this mathematical model. Utilizing the finite element method and deformable grid, the motility of the mutant cilium that is induced by various dynein activation hypotheses was investigated and compared to experimental observation. Results: The results indicate that for the inv mutant, simulations of the ciliary movement with the engagement of dyneins based on the distance-controlled pattern in the partially activation scenario are broadly consistent with the observation; the shortening of the microtubules induces smaller movement amplitudes, while the angles of the mislocalized microtubules affect the pattern of the ciliary movement, and during the ciliary movement, the microtubules swing and twist in the mutant ciliary body. Conclusion: More generally, this study implies that dynein engagement is sensitive to subtle geometric changes in the axoneme, and thus, this geometry greatly influences the integrity of a well-formed ciliary rotation. [ABSTRACT FROM AUTHOR]
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- 2018
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31. Correction: Genome-wide association study of fish oil supplementation on lipid traits in 81,246 individuals reveals new gene-diet interaction loci.
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Francis, Michael, Li, Changwei, Sun, Yitang, Zhou, Jingqi, Li, Xiang, Brenna, J. Thomas, and Ye, Kaixiong
- Subjects
GENOME-wide association studies ,FISH oils ,LOCUS (Genetics) ,DIETARY supplements ,LIPIDS ,GENOMICS - Abstract
Reference 1 Francis M, Li C, Sun Y, Zhou J, Li X, Brenna JT, et al. (2021) Genome-wide association study of fish oil supplementation on lipid traits in 81,246 individuals reveals new gene-diet interaction loci. The ARIC datasets used for the analyses in this manuscript were obtained from dbGaP through dbGaP accession study number phs000280.v3.p1. [Extracted from the article]
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- 2023
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32. Effective estimation of the minimum number of amino acid residues required for functional divergence between duplicate genes.
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Zhou, Jingqi, Liu, Dangyun, Sa, Zhining, Huang, Wei, Zou, Yangyun, and Gu, Xun
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AMINO acid residues , *CHROMOSOME duplication , *PARALOGISM , *BIOLOGICAL divergence , *GENETICS - Abstract
One of hot research foci has always been predicting amino acid residues underlying functional divergence after gene duplication, as those predicted sites can be used as candidates for further functional experimentations. It is important and interesting to know how many sites, on average, may have been responsible for the functional divergence between duplicate genes. In this article, we studied two basic types of functional divergence (type-I and type-II) in depth in order to give an accurate estimation of functional divergence-related sites. Type-I divergences result from altered functional constraints (i.e., different evolutionary rates) between duplicate genes, whereas type-II divergences refer to residues that are conserved by functional constraints but exhibit different physicochemical properties (e.g., charge or hydrophobicity) between duplicates. An effective site number (N E ) strategy was applied in our study, which implements a stepwise regression model to calculate the minimum number of residues responsible for functional divergence without choosing preset threshold. We found that N E -determined cut-off value varies among different duplicate pairs, suggesting that empirical cutoff value is not suitable for every case. Under our standard N E calculation method, we estimated less than 15% of residues that are required for paralogous gene functional divergence. Finally, we established a database, DIVERGE-D, as a public resource for the predicted N E sites between two paralogs in this study, which can be used as candidates for further biological engineering and experimentation. [ABSTRACT FROM AUTHOR]
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- 2017
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33. White Blood Cells and Severe COVID-19: A Mendelian Randomization Study.
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Sun, Yitang, Zhou, Jingqi, Ye, Kaixiong, and Rizzieri, David
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LEUCOCYTES , *COVID-19 , *LEUKOCYTE count , *BASOPHILS - Abstract
Increasing evidence shows that white blood cells are associated with the risk of coronavirus disease 2019 (COVID-19), but the direction and causality of this association are not clear. To evaluate the causal associations between various white blood cell traits and the COVID-19 susceptibility and severity, we conducted two-sample bidirectional Mendelian Randomization (MR) analyses with summary statistics from the largest and most recent genome-wide association studies. Our MR results indicated causal protective effects of higher basophil count, basophil percentage of white blood cells, and myeloid white blood cell count on severe COVID-19, with odds ratios (OR) per standard deviation increment of 0.75 (95% CI: 0.60–0.95), 0.70 (95% CI: 0.54–0.92), and 0.85 (95% CI: 0.73–0.98), respectively. Neither COVID-19 severity nor susceptibility was associated with white blood cell traits in our reverse MR results. Genetically predicted high basophil count, basophil percentage of white blood cells, and myeloid white blood cell count are associated with a lower risk of developing severe COVID-19. Individuals with a lower genetic capacity for basophils are likely at risk, while enhancing the production of basophils may be an effective therapeutic strategy. [ABSTRACT FROM AUTHOR]
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- 2021
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34. The Causal Effects of Blood Iron and Copper on Lipid Metabolism Diseases: Evidence from Phenome-Wide Mendelian Randomization Study.
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Zhou, Jingqi, Liu, Chang, Francis, Michael, Sun, Yitang, Ryu, Moon-Suhn, Grider, Arthur, and Ye, Kaixiong
- Abstract
Blood levels of iron and copper, even within their normal ranges, have been associated with a wide range of clinical outcomes. The available epidemiological evidence for these associations is often inconsistent and suffers from confounding and reverse causation. This study aims to examine the causal clinical effects of blood iron and copper with Mendelian randomization (MR) analyses. Genetic instruments for the blood levels of iron and copper were curated from existing genome-wide association studies. Candidate clinical outcomes were identified based on a phenome-wide association study (PheWAS) between these genetic instruments and a wide range of phenotypes in 310,999 unrelated individuals of European ancestry from the UK Biobank. All signals passing stringent correction for multiple testing were followed by MR analyses, with replication in independent data sources where possible. We found that genetically predicted higher blood levels of iron and copper are both associated with lower risks of iron deficiency anemia (odds ratio (OR) = 0.75, 95% confidence interval (CI): 0.67–0.85, p = 1.90 × 10
−6 for iron; OR = 0.88, 95% CI: 0.78–0.98, p = 0.032 for copper), lipid metabolism disorders, and its two subcategories, hyperlipidemia (OR = 0.90, 95% CI: 0.85–0.96, p = 6.44 × 10−4 ; OR = 0.92, 95% CI: 0.87–0.98, p = 5.51 × 10−3 ) and hypercholesterolemia (OR = 0.90, 95% CI: 0.84–0.95, p = 5.34 × 10−4 ; OR = 0.93, 95% CI: 0.89–0.99, p = 0.022). Consistently, they are also associated with lower blood levels of total cholesterol and low-density lipoprotein cholesterol. Multiple sensitivity tests were applied to assess the presence of pleiotropy and the robustness of causal estimates. Regardless of the approaches, consistent evidence was obtained. Moreover, the unique clinical effects of each blood mineral were identified. Notably, genetically predicated higher blood iron is associated with an enhanced risk of varicose veins (OR = 1.28, 95% CI: 1.15–1.42, p = 4.34 × 10−6 ), while blood copper is positively associated with the risk of osteoarthrosis (OR = 1.07, 95% CI: 1.02–1.13, p = 0.010). Sex-stratified MR analysis further revealed some degree of sex differences in their clinical effects. Our comparative PheWAS-MR study of iron and copper comprehensively characterized their shared and unique clinical effects, highlighting their potential causal roles in hyperlipidemia and hypercholesterolemia. Given the modifiable nature of blood mineral status and the potential for clinical intervention, these findings warrant further investigation. [ABSTRACT FROM AUTHOR]- Published
- 2020
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35. Polysaccharides from Chrysanthemun indicum L. enhance the accumulation of polysaccharide and atractylenolide in Atractylodes macrocephala Koidz.
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Zhou, Yulei, Lu, Xiaofang, Chen, Lei, Zhang, Peifeng, Zhou, Jingqi, Xiong, Qianwen, Shen, Yirui, and Tian, Wei
- Subjects
- *
CHINESE medicine , *PLANT defenses , *PLANT growth , *HERBS , *AGRICULTURAL productivity , *BIOACTIVE compounds - Abstract
Atractylodes macrocephala Koidz. (AM), an herb of traditional Chinese medicine, is well-known for anti-oxidant, anti-tumor and immune regulation potential. However, it is low bioactive compound content that restricts the application of this species. Elicitation is considered as an effective method to enhance biomass and bioactive compound in plants. Our precious study found that polysaccharide of Chrysanthemun indicum L. could promote plant growth by triggering plant defense. In the present study, polysaccharide of Chrysanthemun indicum L. is used to stimulate the accumulation of biomass and bioactive compound with different concentration in Atractylodes macrocephala Koidz. during pot, plot and field experiments. The results suggested that polysaccharide of Chrysanthemun indicum L. could significantly enhance the accumulation of biomass, atractylenolides and polysacchrides. Moreover, 2 mg/mL is determined and verified to be the appropriate concentration during field experiments. In addition, RT-qPCR revealed that CIP-induced terpenoid synthesis in AM mainly depended on mevalonate (MVA) pathway. This is the first report on the discovery of polysaccharide of Chrysanthemun indicum L. for the enhanced accumulation of biaomass and bioactive compound and the use of its for agricultural production. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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36. Plumeriapropionics A-E, Carboxyl-Substituted Phenylpropionic Acid Derivatives with Anti-Inflammatory Activity from Plumeria rubra L.
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Zhou X, Gan M, Wu M, Zheng T, Enkhchimeg C, Li H, Feng S, Zhou J, and Song X
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- Animals, Mice, Flowers, Lipopolysaccharides pharmacology, Nitric Oxide, Organic Chemicals, Anti-Inflammatory Agents pharmacology, Apocynaceae
- Abstract
Five rare carboxyl-substituted phenylpropionic acid derivatives, plumeriapropionics A-E ( 1 - 5 ), together with one known analog, cerberic acid B ( 6 ), were isolated from flowers of Plumeria rubra L. Their structures were elucidated using comprehensive spectroscopic methods. To date, only one compound of this structural type has been reported. The inhibitory activities of compounds 1 - 6 against nitric oxide (NO) production induced by lipopolysaccharide (LPS) were evaluated in vitro using mouse macrophage RAW264.7 cells. Compounds 1 - 6 showed remarkable inhibitory activities on NO production, with IC
50 values in the range of 6.52 ± 0.23 to 35.68 ± 0.17 µM. These results indicate that the discovery of carboxyl-substituted phenylpropionic acid derivatives from the flowers of P. rubra , which show significant anti-inflammatory properties, could be of great importance for the research and development of novel natural anti-inflammatory agents.- Published
- 2023
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37. Associations of metabolic dysfunction-associated fatty liver disease and hepatic fibrosis with bone mineral density and risk of osteopenia/osteoporosis in T2DM patients.
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Zhang W, Li Y, Li S, Zhou J, Wang K, Li Z, Chen N, and Chen X
- Subjects
- Humans, Bone Density, Liver Cirrhosis complications, Liver Cirrhosis epidemiology, Diabetes Mellitus, Type 2 complications, Osteoporosis etiology, Osteoporosis complications, Bone Diseases, Metabolic epidemiology, Bone Diseases, Metabolic etiology, Non-alcoholic Fatty Liver Disease complications, Non-alcoholic Fatty Liver Disease epidemiology
- Abstract
Background: Existing evidence on the associations of liver steatosis and fibrosis with bone mineral density (BMD) and risk of osteopenia/osteoporosis was limited with conflicting results. We aimed to evaluate the associations of metabolic dysfunction-associated fatty liver disease (MAFLD) and hepatic fibrosis with BMD and risk of osteopenia/osteoporosis in type 2 diabetes mellitus (T2DM) patients., Methods: Baseline information of an ongoing cohort of 249 T2DM patients in Xiamen, China was analyzed. MAFLD was defined as the presence of hepatic steatosis [diagnosed by either hepatic ultrasonography scanning or fatty liver index (FLI) score >60] for T2DM patients. BMD was measured using dual-energy x-ray absorptiometry at total lumbar (L2-4), femur neck (FN), and total hip (TH) and was categorized as normal (T ≥ -1.0), osteopenia (-2.5 < T < -1.0), or osteoporosis (T ≤ -2.5) according to its minimum T-score., Results: Among the 249 T2DM patients, prevalence rates of MAFLD, osteopenia, and osteoporosis were 57.8%, 50.6%, and 17.7%, respectively. Patients with MAFLD had significantly higher BMD T-scores of L2-4, FN, and TH and the minimum as well as lower prevalence of osteoporosis than patients without MAFLD. Hepatic steatosis indices, including FLI score, fatty liver (FLI ≥ 60 or hepatic ultrasonography scanning), and MAFLD, were significantly and positively associated with all T-scores, while hepatic fibrosis index and FIB-4 score, but not NAFLD fibrosis score (NFS), were negatively associated with all T-scores. MAFLD was significantly associated with the decreased risk of osteopenia/osteoporosis and osteoporosis with unadjusted odds ratios (ORs) (95% CI) of 0.565 (0.324-0.987) and 0.434 (0.224-0.843) (both p -values < 0.05), respectively. As for liver fibrosis, FIB-4 score, but not NFS, was significantly associated with elevated risk of osteoporosis with an unadjusted OR (95% CI) per SD increase of FIB-4 score of 1.446 (1.080-1.936, p -value = 0.013). Adjusting for potential confounding variables, especially body mass index, in the multivariable regression analyses, all associations of hepatic steatosis and fibrosis indices with BMD and risk of osteopenia/osteoporosis were not statistically significant., Conclusion: MAFLD and hepatic fibrosis were not significantly associated with BMD and risk of osteopenia/osteoporosis independent of obesity. Nevertheless, screening and management of MAFLD and osteopenia/osteoporosis were still important for the prevention of fracture in T2DM patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Li, Li, Zhou, Wang, Li, Chen and Chen.)
- Published
- 2023
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38. A pharmacokinetic analysis of amisulpride in adult Chinese patients with schizophrenia: Impact of creatinine clearance.
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Liu W, Zhou J, Cao M, Zhang F, and Sun X
- Abstract
Objective: To develop a stable population pharmacokinetic (PPK) model of amisulpride and to investigate the effects of covariates on the pharmacokinetic parameters in adult Chinese patients with schizophrenia., Materials and Methods: This retrospective study was carried out using 168 serum samples from 88 patients collected during routine clinical monitoring. Covariates recorded included demographic parameters (gender, age, weight), clinical parameters (serum creatinine, creatinine clearance), and intake of co-medications. The amisulpride PPK model was established using a nonlinear mixed effects modeling (NONMEM) approach. Goodness-of-fit (GOF) plots, bootstrap validation (1,000 runs), and normalized prediction distribution error (NPDE) were used in the evaluation of the final model., Results: A one-compartment model with first-order absorption and elimination was developed. The population estimates for apparent clearance (CL/F) and apparent volume of distribution (V/F) were 32.6 L/h and 391 L, respectively. Estimated creatinine clearance (eCLcr) was a significant covariate for CL/F. The established model was: CL/F = 32.6 × (eCLcr/114.3)0.485 (L/h). The stability of the model was confirmed using GOF plots, bootstrap, and NPDE., Conclusion: Creatinine clearance is a major covariate which is positively correlated with CL/F. Therefore, additional dose adjustments of amisulpride may be required on the basis of eCLcr. An ethnic difference may exist in the pharmacokinetics of amisulpride, but further research is needed in order to confirm this possibility. The PPK model of amisulpride for adult Chinese schizophrenic patients established here using NONMEM, is potentially an important tool for individualizing drug dosage and therapeutic drug monitoring.
- Published
- 2023
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39. Non-obese or lean non-alcoholic fatty liver disease was associated with increased risk of cancer in patients with type 2 diabetes mellitus.
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Chen N, Zhou J, Wang K, Li X, and Li Z
- Subjects
- Humans, Overweight complications, Thinness complications, Thinness epidemiology, Cross-Sectional Studies, Obesity complications, Non-alcoholic Fatty Liver Disease complications, Non-alcoholic Fatty Liver Disease epidemiology, Non-alcoholic Fatty Liver Disease diagnosis, Diabetes Mellitus, Type 2 complications, Neoplasms
- Abstract
Introduction: Risk of non-obese or lean non-alcoholic fatty liver disease (NAFLD) for cancer in patients with type 2 diabetes mellitus (T2DM) is less known. We aimed to evaluate independent associations of NAFLD, especially non-obese or lean NAFLD, and body mass index (BMI) on risks of cancer in patients with T2DM., Research Design and Methods: Cross-sectional analyses of baseline information on a cohort of 233 patients with T2DM were conducted in Xiamen, China. NAFLD was identified by hepatic ultrasonography diagnosis of hepatic steatosis without excessive alcohol consumption, viral or autoimmune liver disease. Fibrosis-4 (FIB-4) score was calculated to quantify severity of hepatic fibrosis., Results: All types of cancers were diagnosed on 19 (8.2%) patients. Prevalence of cancer was significantly higher in those with NAFLD than those without (15.5% vs 4.0%, p=0.002), but were not significantly different among BMI categories (6.8%, 13.7% and 6.5% for those with underweight or normal weight (n=74), overweight (n=51) and obesity (n=108), respectively, p=0.258). With adjustment for potential confounding factors in the multivariable logistic regression models, NAFLD was significantly associated with increased risk of cancer with the adjusted OR (95% CI) of 5.969 (1.349 to 26.413, p=0.019). Stratified analyses across BMI categories found similar association of NAFLD with risk of cancer for those non-obese or lean (the adjusted OR (95% CI) 17.446 (1.690 to 180.095, p=0.016)) but not for those with either overweight (OR (95% CI) 11.642 (0.832 to 162.963, p=0.068) or obesity (OR (95% CI) 0.917 (0.170 to 4.954, p=0.920). FIB-4 score was not significantly associated with risk of cancer for all subjects or stratified across BMI categories. BMI was not significantly associated with risk of cancer for all patients or stratified by NAFLD., Conclusions: NAFLD, even non-obese or lean NAFLD, was independently associated with increased risk of cancer in patients with T2DM. Screening and management of NAFLD, especially for those with underweight or normal weight, should be strengthened from the perspective of improving prevention and management of cancer in patients with T2DM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
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40. Evolution of a chordate-specific mechanism for myoblast fusion.
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Zhang H, Shang R, Kim K, Zheng W, Johnson CJ, Sun L, Niu X, Liu L, Zhou J, Liu L, Zhang Z, Uyeno TA, Pei J, Fissette SD, Green SA, Samudra SP, Wen J, Zhang J, Eggenschwiler JT, Menke DB, Bronner ME, Grishin NV, Li W, Ye K, Zhang Y, Stolfi A, and Bi P
- Abstract
Vertebrate myoblast fusion allows for multinucleated muscle fibers to compound the size and strength of mononucleated cells, but the evolution of this important process is unknown. We investigated the evolutionary origins and function of membrane-coalescing agents Myomaker and Myomixer in various groups of chordates. Here, we report that Myomaker likely arose through gene duplication in the last common ancestor of tunicates and vertebrates, while Myomixer appears to have evolved de novo in early vertebrates. Functional tests revealed a complex evolutionary history of myoblast fusion. A prevertebrate phase of muscle multinucleation driven by Myomaker was followed by the later emergence of Myomixer that enables the highly efficient fusion system of vertebrates. Evolutionary comparisons between vertebrate and nonvertebrate Myomaker revealed key structural and mechanistic insights into myoblast fusion. Thus, our findings suggest an evolutionary model of chordate fusogens and illustrate how new genes shape the emergence of novel morphogenetic traits and mechanisms.
- Published
- 2022
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41. Global, Regional, and National Levels and Trends in the Burden of Pressure Ulcer from 1990 to 2019: A Systematic Analysis for the Global Burden of Disease 2019.
- Author
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Yakupu A, Wang H, Huang L, Zhou J, Wu F, Lu Y, and Lu S
- Abstract
Pressure ulcer (PU) is a type of chronic ulcer, placing a high burden not only on patients' families but also on national healthcare systems globally. To determine the level, trends, and burden of PU worldwide and to provide an essential foundation for building targeted public policies on PUs at the national, regional, and global levels, data on PU were obtained from the Global Burden of Disease (GBD) 2019 Study. The incidence, disability-adjusted life years (DALYs), and deaths of PUs in 204 countries and regions from 1990 to 2019 were calculated and stratified by sex, age, geographical location, and sociodemographic index (SDI). The estimated annual percentage change (EAPC) of incidence, DALYs, and deaths was calculated to evaluate the temporal trends. A total of 3,170,796 new cases (95% uncertainty interval (UI), 3,499,729-2,875,433 cases) of PU were identified globally in 2019, more than 55% of which were among male individuals, and most of the new cases were concentrated in those 75-90 years of age. The burden of PU measured in DALYs was 481 423 (95% UI, 583 429-374 334) in 2019, 73% and 27% of which could be attributed to years of life lost (YLLs) and years lived with disability (YLDs), respectively. The burden increased gradually from 1990 to 2019 (from 267 846 [360 562-211 024] to 481 423 [95% UI, 583 429-374 334]). A total of 24 389 deaths were attributed to PU (95% UI, 31 260.82-17 299). The EAPC of incidence, DALYs, and deaths were negative in most regions, the age-standardized rate (ASR) of incidence, DALYs, and deaths were considered to be decreasing in most of the regions, and the EAPCs were negatively correlated with the SDI levels, universal health coverage (UHC), and gross domestic product (GDP), which shows that the ASRs of PU decreased as the economy developed and countries' healthcare system performances improved.
- Published
- 2022
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42. Comparative Transcriptome Analyses Reveal the Role of Conserved Function in Electric Organ Convergence Across Electric Fishes.
- Author
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Liu A, He F, Zhou J, Zou Y, Su Z, and Gu X
- Abstract
The independent origins of multiple electric organs (EOs) of fish are fascinating examples of convergent evolution. However, comparative transcriptomics of different electric fish lineages are scarce. In this study, we found that the gene expression of EOs and skeletal muscles from three lineages (Mormyroidea, Siluriformes, and Gymnotiformes) tended to cluster together based on the species of origin, irrespective of the organ from which they are derived. A pairwise comparison of differentially expressed genes (DEGs) revealed that no less than half of shared DEGs exhibited parallel expression differentiation, indicating conserved directionality of differential expression either in or between lineages, but only a few shared DEGs were identified across all focal species. Nevertheless, the functional enrichment analysis of DEGs indicated that there were more parallel gene expression changes at the level of pathways and biological functions. Therefore, we may conclude that there is no parallel evolution of the entire transcriptomes of EOs among different lineages. Further, our results support the hypothesis that it is not different genes but conserved biological functions that play a crucial role in the convergence of complex phenotypes. This study provides insight into the genetic basis underlying the EO convergent evolution; however, more studies in different cases will be needed to demonstrate whether this pattern can be extended to other cases to derive a general rule for convergent evolution.
- Published
- 2019
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43. The prognostic signature of the somatic mutations in Ewing sarcoma: from a network view.
- Author
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Zhang Y, Song J, Shi Q, Song X, Shen L, Zhou J, and Shao J
- Subjects
- Cell Line, Tumor, Cluster Analysis, Female, Gene Expression Regulation, Neoplastic, Humans, Male, Mutation Rate, Oncogene Proteins, Fusion genetics, Prognosis, Proportional Hazards Models, Proto-Oncogene Protein c-fli-1 genetics, RNA-Binding Protein EWS genetics, Sarcoma, Ewing pathology, Survival Analysis, Gene Regulatory Networks, Mutation genetics, Sarcoma, Ewing genetics
- Abstract
Background: Ewing sarcoma is a malignant bone tumor mainly affecting teenagers and young adults. Its main driver mutation, the EWS-FLI1 fusion gene, has been identified more than 20 years ago, whereas its other somatic mutations have been just recently reported., Methods: In this study, we organized the somatic mutations from 216 Ewing sarcoma cases into 216 individual protein-protein interaction networks by using interactome information. These mutation networks were then classified into five different clusters based on their structural similarities. The prognostic effect of mutation genes was evaluated according to their network features., Results: The cases in cluster two exhibited remarkably high metastasis and mortality rates, and STAG2, TP53 and TTN were the three most significantly mutated genes in this cluster. Microarray data demonstrate that the expression of STAG2, TP53 and TTN are down-regulated in the EWS-FLI1-knockdown Ewing sarcoma cells. However, the mutation effect analysis shows that the somatic mutations in TTN are less damaging than those in STAG2 and TP53. The analyses of functional network modules further revealed that STAG2, TP53 and their interacting gene partners participate in the oncogenic-related biological modules such as cell cycle and regulation of transcription from RNA polymerase II promoter while TTN, TP53 and their interacting gene partners constitute the modules less relevant to oncogenesis. The results of Gene Ontology analyses demonstrated that the uniquely mutated genes associated with poor prognosis in Clusters 1, 4 and 5 were distinctively enriched in epidermal growth factor-related functions and phosphoproteins., Conclusions: Our study identified the highly lethal mutation combination cases and characterized the possible prognostic genes in Ewing sarcoma from a network perceptive., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2019
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44. XBSeq2: a fast and accurate quantification of differential expression and differential polyadenylation.
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Liu Y, Wu P, Zhou J, Johnson-Pais TL, Lai Z, Chowdhury WH, Rodriguez R, and Chen Y
- Subjects
- Algorithms, Carcinoma, Renal Cell genetics, Databases, Nucleic Acid, Gene Expression Regulation, Neoplastic, High-Throughput Nucleotide Sequencing methods, Humans, Kidney Neoplasms genetics, ROC Curve, Sequence Analysis, RNA, Statistics as Topic, Gene Expression Profiling methods, Polyadenylation genetics, Software
- Abstract
Background: RNA sequencing (RNA-seq) is a high throughput technology that profiles gene expression in a genome-wide manner. RNA-seq has been mainly used for testing differential expression (DE) of transcripts between two conditions and has recently been used for testing differential alternative polyadenylation (APA). In the past, many algorithms have been developed for detecting differentially expressed genes (DEGs) from RNA-seq experiments, including the one we developed, XBSeq, which paid special attention to the context-specific background noise that is ignored in conventional gene expression quantification and DE analysis of RNA-seq data., Results: We present several major updates in XBSeq2, including alternative statistical testing and parameter estimation method for detecting DEGs, capacity to directly process alignment files and methods for testing differential APA usage. We evaluated the performance of XBSeq2 against several other methods by using simulated datasets in terms of area under the receiver operating characteristic (ROC) curve (AUC), number of false discoveries and statistical power. We also benchmarked different methods concerning execution time and computational memory consumed. Finally, we demonstrated the functionality of XBSeq2 by using a set of in-house generated clear cell renal carcinoma (ccRCC) samples., Conclusions: We present several major updates to XBSeq. By using simulated datasets, we demonstrated that, overall, XBSeq2 performs equally well as XBSeq in terms of several statistical metrics and both perform better than DESeq2 and edgeR. In addition, XBSeq2 is faster in speed and consumes much less computational memory compared to XBSeq, allowing users to evaluate differential expression and APA events in parallel. XBSeq2 is available from Bioconductor: http://bioconductor.org/packages/XBSeq/.
- Published
- 2017
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45. Paralog-divergent Features May Help Reduce Off-target Effects of Drugs: Hints from Glucagon Subfamily Analysis.
- Author
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Sa Z, Zhou J, Zou Y, Su Z, and Gu X
- Subjects
- Amino Acid Sequence, Animals, Binding Sites, Diabetes Mellitus, Type 2, Glucagon-Like Peptide-1 Receptor antagonists & inhibitors, Glucagon-Like Peptide-1 Receptor classification, Humans, Molecular Dynamics Simulation, Pharmaceutical Preparations chemistry, Phylogeny, Protein Structure, Tertiary, Pyrazoles chemistry, Pyrazoles metabolism, Receptors, Glucagon antagonists & inhibitors, Receptors, Glucagon classification, Sequence Alignment, beta-Alanine analogs & derivatives, beta-Alanine chemistry, beta-Alanine metabolism, Glucagon-Like Peptide-1 Receptor metabolism, Pharmaceutical Preparations metabolism, Receptors, Glucagon metabolism
- Abstract
Side effects from targeted drugs remain a serious concern. One reason is the nonselective binding of a drug to unintended proteins such as its paralogs, which are highly homologous in sequences and have similar structures and drug-binding pockets. To identify targetable differences between paralogs, we analyzed two types (type-I and type-II) of functional divergence between two paralogs in the known target protein receptor family G-protein coupled receptors (GPCRs) at the amino acid level. Paralogous protein receptors in glucagon-like subfamily, glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), exhibit divergence in ligands and are clinically validated drug targets for type 2 diabetes. Our data showed that type-II amino acids were significantly enriched in the binding sites of antagonist MK-0893 to GCGR, which had a radical shift in physicochemical properties between GCGR and GLP-1R. We also examined the role of type-I amino acids between GCGR and GLP-1R. The divergent features between GCGR and GLP-1R paralogs may be helpful in their discrimination, thus enabling the identification of binding sites to reduce undesirable side effects and increase the target specificity of drugs., (Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)
- Published
- 2017
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46. Mutation-profile-based methods for understanding selection forces in cancer somatic mutations: a comparative analysis.
- Author
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Zhou Z, Zou Y, Liu G, Zhou J, Wu J, Zhao S, Su Z, and Gu X
- Abstract
Human genes exhibit different effects on fitness in cancer and normal cells. Here, we present an evolutionary approach to measure the selection pressure on human genes, using the well-known ratio of the nonsynonymous to synonymous substitution rate in both cancer genomes ( C
N / CS ) and normal populations ( pN / pS ). A new mutation-profile-based method that adopts sample-specific mutation rate profiles instead of conventional substitution models was developed. We found that cancer-specific selection pressure is quite different from the selection pressure at the species and population levels. Both the relaxation of purifying selection on passenger mutations and the positive selection of driver mutations may contribute to the increased CN / CS values of human genes in cancer genomes compared with the pN / pS values in human populations. The CN / CS values also contribute to the improved classification of cancer genes and a better understanding of the onco-functionalization of cancer genes during oncogenesis. The use of our computational pipeline to identify cancer-specific positively and negatively selected genes may provide useful information for understanding the evolution of cancers and identifying possible targets for therapeutic intervention., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.- Published
- 2017
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