159 results on '"Cai, Xue"'
Search Results
2. Enhancing the Thermal Stability and Enzyme Activity of Ketopantoate Hydroxymethyltransferase through Interface Modification Engineering
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Cai, Xue, Shi, Xue, Wang, Jia-Ying, Hu, Cheng-Hao, Shen, Ji-Dong, Zhang, Bo, Liu, Zhi-Qiang, and Zheng, Yu-Guo
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Ketopantoate hydroxymethyltransferase (KPHMT) plays a pivotal role in d-pantothenic acid biosynthesis. Most KPHMTs are homodecamers with low thermal stability, posing challenges for protein engineering and limiting output enhancement. Previously, a high-enzyme activity KPHMT mutant (K25A/E189S) from Corynebacterium glutamicumwas screened as mother strain (M0). Building upon this strain, our study focused on interface engineering modifications, employing a multifaceted approach including integrating folding-free energy calculation, B-factor analysis, and conserved site analysis. Preliminary screening led to the selection of five mutants in the interface─E106S, E98T, E98N, S247I, and S247D─showing improved thermal stability, culminating in the double-site mutant M8 (M0-E98N/S247D). M8 exhibited a T1/2value of 288.79 min at 50 °C, showing a 3.29-fold increase compared to M0. Meanwhile, the Tmvalue of M8 was elevated from 53.2 to 59.6 °C. Investigations of structural and molecular dynamics simulations revealed alterations in surface electrostatic charge distribution and the formation of increased hydrogen bonds between subunits, contributing to enhanced thermal stability. This investigation corroborates the efficacy of interface engineering modifications in bolstering KPHMT stability while showing its potential for positively impacting industrial d-pantothenic acid synthesis.
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- 2024
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3. Muscle Quality in Relation to Prediabetes Phenotypes: A Population-Based Study With Mediation Analysis
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Qiu, Shanhu, Cai, Xue, Zhou, Xiaoying, Xu, Jinshui, Sun, Zilin, Guo, Haijian, and Wu, Tongzhi
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- 2024
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4. Noninvasive Vagus Nerve Stimulation in Postural Tachycardia Syndrome
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Stavrakis, Stavros, Chakraborty, Praloy, Farhat, Kassem, Whyte, Seabrook, Morris, Lynsie, Abideen Asad, Zain Ul, Karfonta, Brittany, Anjum, Juvaria, Matlock, H. Greg, Cai, Xue, and Yu, Xichun
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Low-level transcutaneous stimulation of the auricular branch of the vagus nerve at the tragus is antiarrhythmic and anti-inflammatory in animals and humans. Preliminary studies show that transcutaneous vagus nerve stimulation (tVNS) is beneficial in animal models of postural tachycardia syndrome (POTS).
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- 2024
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5. A wireless optoelectronic probe to monitor oxygenation in deep brain tissue
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Cai, Xue, Zhang, Haijian, Wei, Penghu, Liu, Quanlei, Sheng, Dawid, Li, Zhen, Zhang, Bozhen, Tang, Guo, Zhao, Wenxin, Ye, Zhongyin, Xue, Zhao, Xie, Yang, Dai, Yang, Wang, Changming, Wang, Yuqi, Fu, Xin, Yin, Lan, Peng, Hongshang, Ding, He, Zhao, Guoguang, and Sheng, Xing
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Real-time detection of tissue oxygenation in the nervous system is crucial in neuroscience studies and clinical diagnostics. Complementary to blood oxygenation levels, the partial pressure of oxygen in brain tissue (pbtO2) plays a key role in regulating local neural activities and metabolism. Here we develop an implantable optoelectronic probe that wirelessly and continuously monitors pbtO2signals in the deep brain of freely moving rodents. The thin-film, microscale implant integrates a light-emitting diode and a photodetector, and is coated with an oxygen-sensitive phosphorescent film. Powered by a battery or an inductive coil, a miniaturized circuit is capable of recording and wirelessly transmitting pbtO2signals. The wireless micro-probe captures cerebral hypoxia states in mice in various scenarios, including altered inspired oxygen concentrations and acute ischaemia. In mouse models with seizures, the micro-probe associates temporal pbtO2variations in multiple brain regions with electrical stimulations applied to the hippocampus. Our probe and method offer important insights into neuroscience studies regarding neurometabolic coupling and pave the way for the clinical application of implantable wireless optoelectronic probes.
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- 2024
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6. Regenerative Braking Control Strategy for Distributed Drive Electric Vehicles Based on Slope and Mass Co-Estimation
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Chen, Zeyu, Xiong, Rui, Cai, Xue, Wang, Zhen, and Yang, Ruixin
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The regenerative braking control strategy of distributed drive electric vehicles (DDEVs) under the varying road slope is investigated in this study. Firstly, vehicle dynamic characteristics at the downhill driving condition are analyzed based on a vehicle dynamics model, and the specific impacts of the road slope on the braking control problem are disclosed. Since the estimate of the slope is related to the vehicle mass, an online co-estimation of the road slope and vehicle mass is proposed based on neural network and least square algorithm. The control lines are adjusted according to the estimation results, and the optimization of power allocation is conducted to achieve the optimal braking torque split among the front motor, rear motor, and hydraulic braking system. Finally, the control scheme of regenerative braking is proposed and evaluated by comparing with the Economic Commission of Europe (ECE)-based strategy and the I-curve strategy. The presented strategy provides better braking performance and higher energy recovery compared with that the traditional methods. The results indicate that energy recovery can be improved by up to 9.62% under certain driving conditions.
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- 2023
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7. Combinatorial Metabolic Engineering of Escherichia coli for Enhanced L‑Cysteine Production: Insights into Crucial Regulatory Modes and Optimization of Carbon-Sulfur Metabolism and Cofactor Availability.
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Yang, Hui, Zhang, Bo, Wu, Zi-Dan, Chen, Li-Feng, Pan, Jia-Yuan, Xiu, Xiao-Ling, Cai, Xue, Liu, Zhi-Qiang, and Zheng, Yu-Guo
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- 2023
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8. Resistance prediction in high‐grade serous ovarian carcinoma with neoadjuvant chemotherapy using data‐independent acquisition proteomics and an ovary‐specific spectral library.
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Qian, Liujia, Zhu, Jianqing, Xue, Zhangzhi, Gong, Tingting, Xiang, Nan, Yue, Liang, Cai, Xue, Gong, Wangang, Wang, Junjian, Sun, Rui, Jiang, Wenhao, Ge, Weigang, Wang, He, Zheng, Zhiguo, Wu, Qijun, Zhu, Yi, and Guo, Tiannan
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High‐grade serous ovarian carcinoma (HGSOC) is the most common subtype of ovarian cancer with 5‐year survival rates below 40%. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is recommended for patients with advanced‐stage HGSOC unsuitable for primary debulking surgery (PDS). However, about 40% of patients receiving this treatment exhibited chemoresistance of uncertain molecular mechanisms and predictability. Here, we built a high‐quality ovary‐specific spectral library containing 130 735 peptides and 10 696 proteins on Orbitrap instruments. Compared to a published DIA pan‐human spectral library (DPHL), this spectral library provides 10% more ovary‐specific and 3% more ovary‐enriched proteins. This library was then applied to analyze data‐independent acquisition (DIA) data of tissue samples from an HGSOC cohort treated with NACT, leading to 10 070 quantified proteins, which is 9.73% more than that with DPHL. We further established a six‐protein classifier by parallel reaction monitoring (PRM) to effectively predict the resistance to additional chemotherapy after IDS (Log‐rank test, P = 0.002). The classifier was validated with 57 patients from an independent clinical center (P = 0.014). Thus, we have developed an ovary‐specific spectral library for targeted proteome analysis, and propose a six‐protein classifier that could potentially predict chemoresistance in HGSOC patients after NACT‐IDS treatment. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Enhanced Enzymatic Hydrolysis of High-Solids Content Corncobs by a Lytic Polysaccharide Monooxygenase from Podospora anserina S Mat+ for Valuable Monosaccharides.
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Cai, Xue, Hua, Jing, Lin, Zhen-Ming, Sun, Chen-Yang, Hu, Chang-Hui, Zhang, Xiaojian, Shen, Ji-Dong, Zhou, Hai-Yan, Wang, Hong-Yan, Chen, Kai-Qian, Chen, De-Shui, Cheng, Xin-Ping, Li, Mian, Liu, Zhi-Qiang, and Zheng, Yu-Guo
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- 2023
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10. Effect of a novel pretreatment on the microtensile bond strength of universal adhesives with dentin.
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Pan, Yixiang, Xu, Jiajia, Cai, Xue, Li, Xiaodong, and Wang, Xiaoyan
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BOND strengths ,DENTIN ,ADHESIVES - Abstract
/purpose : The quality of the hybrid layer is of great importance for dentin bonding. The purpose of this study was to develop a novel copper-based pretreatment and investigate the effect of the pretreatment combined with universal adhesives on the dentin bond strength. Etch-and-rinse adhesive Single Bond 2 (SB2) and two universal adhesives Prime Bond Universal (PBU) and Single Bond Universal (SBU) were selected. The dentin surfaces were pretreated with CuSO 4 solution and K 2 HPO 4 solution in turn (Cu–P pretreatment), and the adhesive was applied following the manufacturer's instructions. There were four groups of Cu–P pretreatment: HH-Cu (1.5 mol/L CuSO 4 + 1.0 mol/L K 2 HPO 4); H–Cu (0.15 mol/L CuSO 4 + 0.1 mol/L K 2 HPO 4); L-Cu (0.015 mol/L CuSO 4 + 0.01 mol/L K 2 HPO 4); and LL-Cu (0.0015 mol/L CuSO 4 + 0.001 mol/L K 2 HPO 4). The microtensile bond strength (μ-TBS) and fracture mode were determined. The dentin surface after pretreatment and the antimicrobial properties of the pretreatment agent were also evaluated. The minimum inhibitory concentration and minimum bactericidal concentration of Cu–P pretreatment were 0.012 mol/L CuSO 4 + 0.008 mol/L K 2 HPO 4. Combined with SB2, the H–Cu and L-Cu groups showed a higher μ-TBS (P < 0.01), while the HH-Cu group showed a lower μ-TBS (P < 0.001), and the LL-Cu group showed a similar μ-TBS with the control group without Cu–P pretreatment. Combined with universal adhesives PBU and SBU, the H–Cu and L-Cu groups also showed significantly increased μ-TBS (P < 0.01). The copper-based pretreatment in combination with universal adhesives improved the dentin microtensile bond strength. [ABSTRACT FROM AUTHOR]
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- 2023
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11. Combinatorial Metabolic Engineering of Escherichia colifor Enhanced L-Cysteine Production: Insights into Crucial Regulatory Modes and Optimization of Carbon-Sulfur Metabolism and Cofactor Availability
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Yang, Hui, Zhang, Bo, Wu, Zi-Dan, Chen, Li-Feng, Pan, Jia-Yuan, Xiu, Xiao-Ling, Cai, Xue, Liu, Zhi-Qiang, and Zheng, Yu-Guo
- Abstract
Microbial production of valuable compounds can be enhanced by various metabolic strategies. This study proposed combinatorial metabolic engineering to develop an effective Escherichia colicell factory dedicated to L-cysteine production. First, the crucial regulatory modes that control L-cysteine levels were investigated to guide metabolic modifications. A two-stage fermentation was achieved by employing multi-copy gene expression, improving the balance between production and growth. Subsequently, carbon flux distribution was further optimized by modifying the C1 unit metabolism and the glycolytic pathway. The modifications of sulfur assimilation demonstrated superior performance of thiosulfate utilization pathways in enhancing L-cysteine titer. Furthermore, the studies focusing on cofactor availability and preference emphasized the vital role of synergistic enhancement of sulfur-carbon metabolism in L-cysteine overproduction. In a 5 L bioreactor, the strain BW15-3/pED accumulated 12.6 g/L of L-cysteine. This work presented an effective metabolic engineering strategy for the development of L-cysteine-producing strains.
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- 2023
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12. Fully Biodegradable and Long-Term Operational Primary Zinc Batteries as Power Sources for Electronic Medicine.
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Huang, Xueying, Hou, Hanqing, Yu, Bingbing, Bai, Jun, Guan, Yanjun, Wang, Liu, Chen, Kuntao, Wang, Xibo, Sun, Pengcheng, Deng, Yuping, Liu, Shangbin, Cai, Xue, Wang, Yu, Peng, Jiang, Sheng, Xing, Xiong, Wei, and Yin, Lan
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- 2023
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13. Spatiotemporal Gene Expression by a Genetic Circuit for Chemical Production in Escherichia coli.
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Zhang, Bo, Yang, Hui, Wu, Zidan, Pan, Jiayuan, Li, Shirong, Chen, Lifeng, Cai, Xue, Liu, Zhiqiang, and Zheng, Yuguo
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- 2023
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14. In2Se3, In2Te3, and In2(Se,Te)3 Alloys as Photovoltaic Materials.
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Li, Wei, Cai, Xue-Fen, Valdes, Nicholas, Wang, Tianshi, Shafarman, William, Wei, Su-Huai, and Janotti, Anderson
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- 2022
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15. Effect of Calcination Atmosphere on the Structure and Catalytic Behavior of Cr2O3/Al2O3 Catalysts for Dehydrogenation of Propane.
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Cai, Xue, Zhang, Zitong, Cai, Lili, Tian, Xiaoyan, Chu, Wenling, and Yang, Weishen
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- 2022
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16. Vitexicarpin suppresses malignant progression of colorectal cancer through affecting c-Myc ubiquitination by targeting IMPDH2.
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Ding, Xiao-Jing, Cai, Xue-Mei, Wang, Qian-Qian, Liu, Ning, Zhong, Wei-Long, Xi, Xiao-Nan, and Lu, Ya-Xin
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• Vitexicarpin significantly suppressed the proliferation, invasion and metastasis of colorectal cancer cells in vitro. • Vitexicarpin inhibited colorectal cancer growth and lung metastasis in vivo without obvious systemic toxicity. • Vitexicarpin promoted the ubiquitination degradation and decreased the level of c-Myc by disrupting the interaction between IMPDH2 and c-Myc and then inhibitd its downstream epithelial-mesenchymal transition process. • IMPDH2 and c-Myc are over-expressed and co-localized in human CRC tissues and CRC cells. Colorectal cancer (CRC) is the second most common cause of cancer-related mortality and is characterised by extensive invasive and metastatic potential. Previous studies have shown that vitexicarpin extracted from the fruits of Vitex rotundifolia can impede tumour progression. However, the molecular mechanisms involved in CRC treatment are still not fully established. Our study aimed to investigate the anticancer activity, targets, and molecular mechanisms of vitexicarpin in CRC hoping to provide novel therapies for patients with CRC. The impact of vitexicarpin on CRC was assessed through various experiments including MTT, clone formation, EDU, cell cycle, and apoptosis assays, as well as a tumour xenograft model. CETSA, label-free quantitative proteomics, and Biacore were used to identify the vitexicarpin targets. WB, Co-IP, Ubiquitination assay, IF, molecular docking, MST, and cell transfection were used to investigate the mechanism of action of vitexicarpin in CRC cells. Furthermore, we analysed the expression patterns and correlation of target proteins in TCGA and GEPIA datasets and clinical samples. Finally, wound healing, Transwell, tail vein injection model, and tissue section staining were used to demonstrate the antimetastatic effect of vitexicarpin on CRC in vitro and in vivo. Our findings demonstrated that vitexicarpin exhibits anticancer activity by directly binding to inosine monophosphate dehydrogenase 2 (IMPDH2) and that it promotes c-Myc ubiquitination by disrupting the interaction between IMPDH2 and c-Myc, leading to epithelial-mesenchymal transition (EMT) inhibition. Vitexicarpin hinders the migration and invasion of CRC cells by reversing EMT both in vitro and in vivo. Additionally, these results were validated by the overexpression and knockdown of IMPDH2 in CRC cells. These results demonstrated that vitexicarpin regulates the interaction between IMPDH2 and c-Myc to inhibit CRC proliferation and metastasis both in vitro and in vivo. These discoveries introduce potential molecular targets for CRC treatment and shed light on new mechanisms for c-Myc regulation in tumours. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Effects of peer support and mobile application-based walking programme on physical activity and physical function in rural older adults: a cluster randomized controlled trial.
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Cai, Xue, Qiu, Shanhu, Luo, Dan, Li, Ruxue, Liu, Chengyu, Lu, Yanhui, Xu, Cuirong, and Li, Mingzi
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Key summary points: Aim: To assess the effectiveness of a 3-month peer support and mobile application-based walking programme on physical activity and physical function in rural older Chinese adults. Findings: (1) Peer support and mobile application-based walking programme increased physical activity and grip strength but not gait speed, chair-rising time, or body composition in rural older Chinese adults. (2) Increases in daily steps were associated with gains in gait speed and decreases in chair-rising time. Message: Peer support and mobile application-based walking programme improved physical activity and physical function in rural older adults. Purpose: Increased physical activity maintains functional fitness and prevents aging-related declines in muscle mass for older adults. However, physical inactivity is prevalent in aging population, particularly in those living in rural areas. In this study we assessed the effectiveness of a 3-month peer support and mobile application-based walking programme on physical activity and physical function in rural older Chinese adults. Methods: This was a cluster randomized control trial recruiting adults aged ≥ 60 years. Participants were randomized into intervention and control groups (4 clusters with 36 participants for each group). The intervention included face-to-face physical activity group sessions, peer-led walking, and mobile application-based feedback. Primary outcome was pedometer-measured daily walking steps, and secondary outcomes mainly included physical function and body composition. Both intention-to-treat and per-protocol analyses were performed. Results: Of the included 72 participants (mean age 66.9 years, male 36.1%), 64 completed the study. Intention-to-treat analysis showed that after 3-month walking programme, physical activity was increased by 408 steps/day and grip strength by 1.25 kg in the intervention group compared with the control group. However, no significant outcomes were observed on gait speed, chair-rising time, or body composition. Per-protocol analysis showed similar results. Linear regression analyses showed that changes in daily steps were associated with changes in gait speed (ß = 0.63, P < 0.001) and chair-rising time (ß = − 0.31, P = 0.01). Conclusions: The 3-month peer support and mobile application-based walking programme could improve physical activity and physical function in rural older adults. Trial registration: ChiCTR2000034842, registered on 2020/07/21. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Conserved and plant-specific histone acetyltransferase complexes cooperate to regulate gene transcription and plant development
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Wu, Chan-Juan, Yuan, Dan-Yang, Liu, Zhen-Zhen, Xu, Xin, Wei, Long, Cai, Xue-Wei, Su, Yin-Na, Li, Lin, Chen, She, and He, Xin-Jian
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Although a conserved SAGA complex containing the histone acetyltransferase GCN5 is known to mediate histone acetylation and transcriptional activation in eukaryotes, how to maintain different levels of histone acetylation and transcription at the whole-genome level remains to be determined. Here we identify and characterize a plant-specific GCN5-containing complex, which we term PAGA, in Arabidopsis thalianaand Oryza sativa. In Arabidopsis, the PAGA complex consists of two conserved subunits (GCN5 and ADA2A) and four plant-specific subunits (SPC, ING1, SDRL and EAF6). We find that PAGA and SAGA can independently mediate moderate and high levels of histone acetylation, respectively, thereby promoting transcriptional activation. Moreover, PAGA and SAGA can also repress gene transcription via the antagonistic effect between PAGA and SAGA. Unlike SAGA, which regulates multiple biological processes, PAGA is specifically involved in plant height and branch growth by regulating the transcription of hormone biosynthesis and response related genes. These results reveal how PAGA and SAGA cooperate to regulate histone acetylation, transcription and development. Given that the PAGA mutants show semi-dwarf and increased branching phenotypes without reduction in seed yield, the PAGA mutations could potentially be used for crop improvement.
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- 2023
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19. Efficient Activity Enhancement of a Lipase from Sporisorium reilianumfor the Synthesis of a Moxifloxacin Chiral Intermediate via Rational Design
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Cai, Xue, Shen, Jiang-Wei, Qiang, Yu, Hua, Jing, Ma, Zhang-Qi, Liu, Zhi-Qiang, and Zheng, Yu-Guo
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Lipase-catalyzed stereoselective resolution of cis-(±)-dimethyl 1-acetylpiperidine-2,3-dicarboxylate (cis-(±)-1) is an attractive route for the synthesis of (S,S)-2,8-diazobicyclo[4.3.0]nonane, an important chiral intermediate of the fluoroquinolone antibiotic, moxifloxacin. In our previous study, a lipase from Sporisorium reilianum(SRL) was identified to possess excellent thermostability and pH stability. However, the low enzymatic activity of the SRL is a challenge that must be addressed. A rational design was initially employed for SRL tailoring according to the engineered Candida antarcticalipase B (CALB), resulting in a beneficial variant called SRL-I194N/V195L. Subsequently, two key amino acid residues in loop 6, L145 and L154, which might modulate the lid conformation between open and closed, were identified. A tetra-site variant, SRL-I194N/V195L/L145V/L154G (V13), with a significantly enhanced activity of 87.8 U∙mg−1was obtained; this value was 2195-fold higher than that of wild-type SRL. Variant V13 was used to prepare optically pure (2S,3R)-dimethyl 1-acetylpiperidine-2,3-dicarboxylate ((2S,3R)-1), resolving 1 mol∙L−1cis-(±)-1 with a conversion of 49.9% in 2 h and absolute stereoselectivity (E > 200). Excellent stability with a half-life of 92.5 h was also observed at 50 °C. Overall, the study findings reveal a lipase with high activity toward cis-(±)-1 at an industrial level and may offer a general strategy for enhancing the enzyme activity of other lipases and other classes of enzymes with a lid moiety.
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- 2022
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20. Comprehensive characterization of three classes of ArabidopsisSWI/SNF chromatin remodelling complexes
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Guo, Jing, Cai, Guang, Li, Yong-Qiang, Zhang, Yi-Xuan, Su, Yin-Na, Yuan, Dan-Yang, Zhang, Zhao-Chen, Liu, Zhen-Zhen, Cai, Xue-Wei, Guo, Jing, Li, Lin, Chen, She, and He, Xin-Jian
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Although SWI/SNF chromatin remodelling complexes are known to regulate diverse biological functions in plants, the classification, compositions and functional mechanisms of the complexes remain to be determined. Here we comprehensively characterized SWI/SNF complexes by affinity purification and mass spectrometry in Arabidopsis thaliana, and found three classes of SWI/SNF complexes, which we termed BAS, SAS and MAS (BRM-, SYD- and MINU1/2-associated SWI/SNF complexes). By investigating multiple developmental phenotypes of SWI/SNF mutants, we found that three classes of SWI/SNF complexes have both overlapping and specific functions in regulating development. To investigate how the three classes of SWI/SNF complexes differentially regulate development, we mapped different SWI/SNF components on chromatin at the whole-genome level and determined their effects on chromatin accessibility. While all three classes of SWI/SNF complexes regulate chromatin accessibility at proximal promoter regions, SAS is a major SWI/SNF complex that is responsible for mediating chromatin accessibility at distal promoter regions and intergenic regions. Histone modifications are related to both the association of SWI/SNF complexes with chromatin and the SWI/SNF-dependent chromatin accessibility. Three classes of SWI/SNF-dependent accessibility may enable different sets of transcription factors to access chromatin. These findings lay a foundation for further investigation of the function of three classes of SWI/SNF complexes in plants.
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- 2022
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21. Rerouting Fluxes of the Central Carbon Metabolism and Relieving Mechanism-Based Inactivation of l‑Aspartate-α-decarboxylase for Fermentative Production of β‑Alanine in Escherichia coli.
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Li, Bo, Zhang, Bo, Wang, Pei, Cai, Xue, Chen, Yuan-Yuan, Yang, Yu-Feng, Liu, Zhi-Qiang, and Zheng, Yu-Guo
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- 2022
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22. metaExpertPro: A Computational Workflow for Metaproteomics Spectral Library Construction and Data-Independent Acquisition Mass Spectrometry Data Analysis
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Sun, Yingying, Xing, Ziyuan, Liang, Shuang, Miao, Zelei, Zhuo, Lai-bao, Jiang, Wenhao, Zhao, Hui, Gao, Huanhuan, Xie, Yuting, Zhou, Yan, Yue, Liang, Cai, Xue, Chen, Yu-ming, Zheng, Ju-Sheng, and Guo, Tiannan
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Analysis of large-scale data-independent acquisition mass spectrometry metaproteomics data remains a computational challenge. Here, we present a computational pipeline called metaExpertPro for metaproteomics data analysis. This pipeline encompasses spectral library generation using data-dependent acquisition MS, protein identification and quantification using data-independent acquisition mass spectrometry, functional and taxonomic annotation, as well as quantitative matrix generation for both microbiota and hosts. By integrating FragPipe and DIA-NN, metaExpertPro offers compatibility with both Orbitrap and timsTOF MS instruments. To evaluate the depth and accuracy of identification and quantification, we conducted extensive assessments using human fecal samples and benchmark tests. Performance tests conducted on human fecal samples indicated that metaExpertPro quantified an average of 45,000 peptides in a 60-min diaPASEF injection. Notably, metaExpertPro outperformed three existing software tools by characterizing a higher number of peptides and proteins. Importantly, metaExpertPro maintained a low factual false discovery rate of approximately 5% for protein groups across four benchmark tests. Applying a filter of five peptides per genus, metaExpertPro achieved relatively high accuracy (F-score = 0.67–0.90) in genus diversity and showed a high correlation (rSpearman = 0.73–0.82) between the measured and true genus relative abundance in benchmark tests. Additionally, the quantitative results at the protein, taxonomy, and function levels exhibited high reproducibility and consistency across the commonly adopted public human gut microbial protein databases IGC and UHGP. In a metaproteomic analysis of dyslipidemia patients, metaExpertPro revealed characteristic alterations in microbial functions and potential interactions between the microbiota and the host.
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- 2024
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23. High-throughput proteomic sample preparation using pressure cycling technology
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Cai, Xue, Xue, Zhangzhi, Wu, Chunlong, Sun, Rui, Qian, Liujia, Yue, Liang, Ge, Weigang, Yi, Xiao, Liu, Wei, Chen, Chen, Gao, Huanhuan, Yu, Jing, Xu, Luang, Zhu, Yi, and Guo, Tiannan
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High-throughput lysis and proteolytic digestion of biopsy-level tissue specimens is a major bottleneck for clinical proteomics. Here we describe a detailed protocol of pressure cycling technology (PCT)-assisted sample preparation for proteomic analysis of biopsy tissues. A piece of fresh frozen or formalin-fixed paraffin-embedded tissue weighing ~0.1–2 mg is placed in a 150 μL pressure-resistant tube called a PCT-MicroTube with proper lysis buffer. After closing with a PCT-MicroPestle, a batch of 16 PCT-MicroTubes are placed in a Barocycler, which imposes oscillating pressure to the samples from one atmosphere to up to ~3,000 times atmospheric pressure. The pressure cycling schemes are optimized for tissue lysis and protein digestion, and can be programmed in the Barocycler to allow reproducible, robust and efficient protein extraction and proteolysis digestion for mass spectrometry-based proteomics. This method allows effective preparation of not only fresh frozen and formalin-fixed paraffin-embedded tissue, but also cells, feces and tear strips. It takes ~3 h to process 16 samples in one batch. The resulting peptides can be analyzed by various mass spectrometry-based proteomics methods. We demonstrate the applications of this protocol with mouse kidney tissue and eight types of human tumors.
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- 2022
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24. Triptycene-Based Porous Chalcogen-Bonded Organic Frameworks.
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Yang, Wei, Jiang, Rong, Liu, Chao, Yu, Baoqiu, Cai, Xue, and Wang, Hailong
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- 2021
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25. Circulating Proteome and Progression of Type 2 Diabetes
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Gou, Wanglong, Yue, Liang, Tang, Xin-yi, Wu, Yan-yan, Cai, Xue, Shuai, Menglei, Miao, Zelei, Fu, Yuanqing, Chen, Hao, Jiang, Zengliang, Wang, Jiali, Tian, Yunyi, Xiao, Congmei, Xiang, Nan, Wu, Zhen, Chen, Yu-ming, Guo, Tiannan, and Zheng, Ju-Sheng
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- 2022
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26. Wireless, battery-free, fully implantable optoelectronic devices and systems for tissue oxygen sensing
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Čižmár, Tomáš, Fellin, Tommaso, Ding, He, Xue, Zhao, Cai, Xue, and Sheng, Xing
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- 2024
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27. Muscle strength and prediabetes progression and regression in middle‐aged and older adults: a prospective cohort study
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Qiu, Shanhu, Cai, Xue, Yuan, Yang, Xie, Bo, Sun, Zilin, Wang, Duolao, and Wu, Tongzhi
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Prediabetes progression is associated with increased mortality while its regression decreases it. It is unclear whether muscle strength is related to prediabetes progression or regression. This study investigated the associations of muscle strength, assessed by grip strength and chair‐rising time, with prediabetes progression and regression based on the China Health and Retirement Longitudinal Study (CHARLS) enrolling middle‐aged and older adults. We included 2623 participants with prediabetes from CHARLS, who were followed up 4 years later with blood samples collected for measuring fasting plasma glucose and haemoglobin A1c. Grip strength (normalized by body weight) and chair‐rising time were assessed at baseline and categorized into tertiles (low, middle, and high groups). Prediabetes at baseline and follow‐up was defined primarily using the American Diabetes Association (ADA) criteria and secondarily using the World Health Organization (WHO) and International Expert Committee (IEC) criteria. Multinomial logistic regression analysis was applied to obtain the odds ratios (ORs) and 95% confidence intervals (CIs). The mean age of included participants was 59.0 ± 8.6 years, and 46.6% of them were males. During follow‐up, 1646 participants remained as prediabetes, 379 progressed to diabetes, and 598 regressed to normoglycaemia based on ADA criteria. Participants who progressed to diabetes had lower normalized grip strength than those who remained as prediabetes (0.49 ± 0.15 vs. 0.53 ± 0.15, P< 0.001), but participants who regressed to normoglycaemia showed the opposite (0.55 ± 0.16 vs. 0.53 ± 0.15, P= 0.003). However, chair‐rising time was comparable across different groups (Poverall= 0.17). Compared with participants in low normalized grip strength or high chair‐rising time group, those in high normalized grip strength or low chair‐rising time group had decreased odds of progression to diabetes (OR 0.62, 95% CI 0.44 to 0.87; and OR 0.69, 95% CI 0.51 to 0.93, respectively) after multivariable adjustment. However, both were unrelated to the odds of regression to normoglycaemia (OR 0.94, 95% CI 0.71 to 1.25; and OR 0.84, 95% CI 0.65 to 1.07, respectively). These outcomes remained generally comparable when prediabetes was defined by WHO or IEC criteria. Higher normalized grip strength but not lower chair‐rising time was prospectively associated with lower blood pressure, better glycaemic condition, and lower inflammation (all P≤ 0.04). High muscle strength is associated with reduced odds of progression to diabetes but does not predict regression to normoglycaemia in prediabetes. Future studies are warranted to assess whether increases in muscle strength promote prediabetes regression.
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- 2022
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28. Structural basis of sphingosine-1-phosphate receptor 1 activation and biased agonism
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Xu, Zhenmei, Ikuta, Tatsuya, Kawakami, Kouki, Kise, Ryoji, Qian, Yu, Xia, Ruixue, Sun, Ming-Xia, Zhang, Anqi, Guo, Changyou, Cai, Xue-Hui, Huang, Zhiwei, Inoue, Asuka, and He, Yuanzheng
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Sphingosine-1-phosphate receptor 1 (S1PR1) is a master regulator of lymphocyte egress from the lymph node and an established drug target for multiple sclerosis (MS). Mechanistically, therapeutic S1PR1 modulators activate the receptor yet induce sustained internalization through a potent association with β-arrestin. However, a structural basis of biased agonism remains elusive. Here, we report the cryo-electron microscopy (cryo-EM) structures of Gi-bound S1PR1 in complex with S1P, fingolimod-phosphate (FTY720-P) and siponimod (BAF312). In combination with functional assays and molecular dynamics (MD) studies, we reveal that the β-arrestin-biased ligands direct a distinct activation path in S1PR1 through the extensive interplay between the PIF and the NPxxY motifs. Specifically, the intermediate flipping of W2696.48and the retained interaction between F2656.44and N3077.49are the key features of the β-arrestin bias. We further identify ligand–receptor interactions accounting for the S1PR subtype specificity of BAF312. These structural insights provide a rational basis for designing novel signaling-biased S1PR modulators.
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- 2022
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29. Remodeling of the Purkinje Network in Congestive Heart Failure in the Rabbit.
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Logantha, Sunil Jit R. J., Cai, Xue J., Yanni, Joseph, Jones, Caroline B., Stephenson, Robert S., Stuart, Luke, Quigley, Gillian, Monfredi, Oliver, Nakao, Shu, Oh, Il-Young, Starborg, Tobias, Kitmitto, Ashraf, Vohra, Akbar, Hutcheon, Robert C., Corno, Antonio F., Jarvis, Jonathan C., Dobrzynski, Halina, Boyett, Mark R., and Hart, George
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BACKGROUND: Purkinje fibers (PFs) control timing of ventricular conduction and play a key role in arrhythmogenesis in heart failure (HF) patients. We investigated the effects of HF on PFs. METHODS: Echocardiography, electrocardiography, micro-computed tomography, quantitative polymerase chain reaction, immunohistochemistry, volume electron microscopy, and sharp microelectrode electrophysiology were used. RESULTS: Congestive HF was induced in rabbits by left ventricular volume- and pressure-overload producing left ventricular hypertrophy, diminished fractional shortening and ejection fraction, and increased left ventricular dimensions. HF baseline QRS and corrected QT interval were prolonged by 17% and 21% (mean±SEMs: 303±6 ms HF, 249±11 ms control; n=8/7; P=0.0002), suggesting PF dysfunction and impaired ventricular repolarization. Micro-computed tomography imaging showed increased free-running left PF network volume and length in HF. mRNA levels for 40 ion channels, Ca2+-handling proteins, connexins, and proinflammatory and fibrosis markers were assessed: 50% and 35% were dysregulated in left and right PFs respectively, whereas only 12.5% and 7.5% changed in left and right ventricular muscle. Funny channels, Ca2+-channels, and K+-channels were significantly reduced in left PFs. Microelectrode recordings from left PFs revealed more negative resting membrane potential, reduced action potential upstroke velocity, prolonged duration (action potential duration at 90% repolarization: 378±24 ms HF, 249±5 ms control; n=23/38; P<0.0001), and arrhythmic events in HF. Similar electrical remodeling was seen at the left PFventricular junction. In the failing left ventricle, upstroke velocity and amplitude were increased, but action potential duration at 90% repolarization was unaffected. CONCLUSIONS: Severe volume- followed by pressure-overload causes rapidly progressing HF with extensive remodeling of PFs. The PF network is central to both arrhythmogenesis and contractile dysfunction and the pathological remodeling may increase the risk of fatal arrhythmias in HF patients. [ABSTRACT FROM AUTHOR]
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- 2021
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30. Potential Use of Serum Proteomics for Monitoring COVID-19 Progression to Complement RT-PCR Detection
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Zhang, Ying, Cai, Xue, Ge, Weigang, Wang, Donglian, Zhu, Guangjun, Qian, Liujia, Xiang, Nan, Yue, Liang, Liang, Shuang, Zhang, Fangfei, Wang, Jing, Zhou, Kai, Zheng, Yufen, Lin, Minjie, Sun, Tong, Lu, Ruyue, Zhang, Chao, Xu, Luang, Sun, Yaoting, Zhou, Xiaoxu, Yu, Jing, Lyu, Mengge, Shen, Bo, Zhu, Hongguo, Xu, Jiaqin, Zhu, Yi, and Guo, Tiannan
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RT-PCR is the primary method to diagnose COVID-19 and is also used to monitor the disease course. This approach, however, suffers from false negatives due to RNA instability and poses a high risk to medical practitioners. Here, we investigated the potential of using serum proteomics to predict viral nucleic acid positivity during COVID-19. We analyzed the proteome of 275 inactivated serum samples from 54 out of 144 COVID-19 patients and shortlisted 42 regulated proteins in the severe group and 12 in the non-severe group. Using these regulated proteins and several key clinical indexes, including days after symptoms onset, platelet counts, and magnesium, we developed two machine learning models to predict nucleic acid positivity, with an AUC of 0.94 in severe cases and 0.89 in non-severe cases, respectively. Our data suggest the potential of using a serum protein-based machine learning model to monitor COVID-19 progression, thus complementing swab RT-PCR tests. More efforts are required to promote this approach into clinical practice since mass spectrometry-based protein measurement is not currently widely accessible in clinic.
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- 2022
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31. Triptycene-Based Porous Chalcogen-Bonded Organic Frameworks
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Yang, Wei, Jiang, Rong, Liu, Chao, Yu, Baoqiu, Cai, Xue, and Wang, Hailong
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Two chalcogen-bonded organic frameworks (denoted as CBOFs), CBOF-1 and CBOF-2, have been constructed by the self-assembly of a custom-made triptycenetris(2,1,3-benzoselendiazole) (TTB) as an organic building block. As revealed by the results of single crystal X-ray diffraction analysis, the combination of chalcogen bonding and Se···π interactions was conductive to the structural porosity of the obtained two compounds. In particular, CBOF-1 exhibited a 3D 4-connected lvttopological framework with TTB simplified as the 4-connected node. The open pore channels of CBOF-1 possessed a pore size of 4.2 Å, of which the theoretical accessible pore volume occupied 35.6% of the total volume. Structural porosity of CBOF-2 was filled by tetrahydrofuran molecules, and the accessible volume percentage was calculated for 29.5%. Due to the flexible structure, degassed CBOF-1 displayed permanent porosity using carbon dioxide as an absorbate at 196 K. In the present study, a new kind of porous organic framework with permanent porosity has been revealed.
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- 2021
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32. Does objectively measured light-intensity physical activity reduce the risk of cardiovascular mortality? A meta-analysis
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Qiu, Shanhu, Cai, Xue, Jia, Lijing, Sun, Zilin, Wu, Tongzhi, Wendt, Janine, Steinacker, Jürgen Michael, and Schumann, Uwe
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Graphical Abstract
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- 2021
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33. Construction of a Silk Fibroin/Polyethylene Glycol Double Network Hydrogel with Co-Culture of HUVECs and UCMSCs for a Functional Vascular Network.
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Chen, Hong, Zhang, Yajie, Ni, Tianyu, Ding, Pi, Zan, Yue, Cai, Xue, Zhang, Yiwei, Liu, Min, and Pei, Renjun
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- 2021
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34. PulseDIA: Data-Independent Acquisition Mass Spectrometry Using Multi-Injection Pulsed Gas-Phase Fractionation.
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Cai, Xue, Ge, Weigang, Yi, Xiao, Sun, Rui, Zhu, Jiang, Lu, Cong, Sun, Ping, Zhu, Tiansheng, Ruan, Guan, Yuan, Chunhui, Liang, Shuang, Lyu, Mengge, Huang, Shiang, Zhu, Yi, and Guo, Tiannan
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- 2021
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35. Theoretical Studies on the Structures of Metal String Complexes Crn(L)4Cl2(n= 3, 5, 7; L = Oligo-α-Pyridylamide) under the Effect of an Electric Field
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Gao, Pan, Cai, Xue-Ping, Xie, Qiongyi, Yang, Qingyun, Ou, Hong, Wu, Wei-Qing, Xu, Xuan, Xu, Zhiguang, and Lin, Xiaoming
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To study the electronic structures and properties of [Crn(L)4Cl2] (n= 3, L = dpa: di(2-pyridyl)amido; n= 5, L = tpda: tripyridyldiamido; n= 7, L = teptra: tetrapyridyltriamine) metal string complexes, the BP86 method was used by considering the influence of the electric field (EF) applied parallel to the metal axis. As the EF increases, the migration of more positively charged Croddis more significant than that of Creven, which results in alternating long–short Cr–Cr bonds. This happens because of the natural charges on the Croddof 1–3, which are more electropositive than those on Creven. The electrons are pulled to the Cr and Cl(r) atoms at the high-potential side from Cl(l) at the low-potential side by the EF, which leads to asymmetrical FMOs. After the critical electric field (Ec), the configuration turns into a remarkably asymmetric one with alternating Cr–Cr quadruple bonds and weak interactions. The electrons are transferred from equatorial ligands (L) to metal chains. In the meantime, the asymmetry of the FMOs increases and the delocalization is further reduced, which affects the conductivity. Especially for [Cr7(teptra)4Cl2], the delocalized electrons of HOMO are completely transformed into a localized model after the critical electric field. It is observed that this supports the electric switching phenomenon ascribed to the conformations of delocalized and localized electrons. In addition, the longer the length of the metal chain, the smaller the Ecand the easier is for the complexes to be polarized by the EF.
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- 2021
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36. Synergistic effects of phases in the selective oxidation of isobutane over supported (NH4)3HPMo11VO40catalysts
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Cai, Xue, Ma, Yue, Zhou, Qi, Zhang, Zitong, Chu, Wenling, and Yang, Weishen
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The supported 40 wt% (NH4)3HPMo11VO40(APMV) catalysts over two different types of supports, supports-I (Cs3PMo12O40, Cs2.5H0.5PMo12O40, Cs4PMo11VO40and Cs3HPMo11VO40) and supports-II (CeO2, WO3/ZrO2and S-1 molecular sieve), were synthesized by deposition–precipitation method and further evaluated in the partial oxidation of isobutane to methacrylic acid (MAA) at 340 °C under atmospheric pressure. The fresh and used catalysts were characterized by N2adsorption/desorption, TG/DTG, XRD, FT-IR, Raman spectroscopy, pyridine- adsorption FT-IR and NH3-TPD to investigate their structure, stability and surface acidity. The better results were obtained by impregnating 40 wt% active APMV phase onto the supports-I phase with same/similar Keggin structure, and it is believed that the formation of coherent interfaces between two structural well-matched phases with the same/similar Keggin anions greatly promotes interfacial transfer abilities of electrons and lattice oxygen, which is responsible for the efficient oxygen insertion to maximize MAA selectivity and conversion of isobutane. The current work provides a concept of phase synergy to design a promising catalyst for selective oxidation of isobutane.
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- 2021
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37. Arabidopsis RPD3-like histone deacetylases form multiple complexes involved in stress response
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Feng, Chao, Cai, Xue-Wei, Su, Yin-Na, Li, Lin, Chen, She, and He, Xin-Jian
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The Arabidopsis thalianaRPD3-type histone deacetylases have been known to form conserved SIN3-type histone deacetylase complexes, but whether they form other types of complexes is unknown. Here, we perform affinity purification followed by mass spectrometry and demonstrate that the Arabidopsis RPD3-type histone deacetylases HDA6 and HDA19 interact with several previously uncharacterized proteins, thereby forming three types of plant-specific histone deacetylase complexes, which we named SANT, ESANT, and ARID. RNA-seq indicates that the newly identified components function together with HDA6 and HDA19 and coregulate the expression of a number of genes. HDA6 and HDA19 were previously thought to repress gene transcription by histone deacetylation. We find that the histone deacetylase complexes can repress gene expression via both histone deacetylation-dependent and -independent mechanisms. In the mutants of histone deacetylase complexes, the expression of a number of stress-induced genes is up-regulated, and several mutants of the histone deacetylase complexes show severe retardation in growth. Considering that growth retardation is thought to be a trade-off for an increase in stress tolerance, we infer that the histone deacetylase complexes identified in this study prevent overexpression of stress-induced genes and thereby ensure normal growth of plants under nonstress conditions.
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- 2021
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38. An implantable optoelectronic probe for monitoring brain tissue oxygenation
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Luo, Qingming, Ding, Jun, Fu, Ling, Cai, Xue, and Sheng, Xing
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- 2024
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39. Defect Dynamic Model of the Synergistic Effect in Neutron- and γ‑Ray-Irradiated Silicon NPN Transistors.
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Song, Yu, Zhou, Hang, Cai, Xue-Fen, Liu, Yang, Yang, Ping, Zhang, Guang-Hui, Zhang, Ying, Lan, Mu, and Wei, Su-Huai
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- 2020
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40. Accelerated Protein Biomarker Discovery from FFPE Tissue Samples Using Single-Shot, Short Gradient Microflow SWATH MS.
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Sun, Rui, Hunter, Christie, Chen, Chen, Ge, Weigang, Morrice, Nick, Liang, Shuang, Zhu, Tiansheng, Yuan, Chunhui, Ruan, Guan, Zhang, Qiushi, Cai, Xue, Yu, Xiaoyan, Chen, Lirong, Dai, Shaozheng, Luan, Zhongzhi, Aebersold, Ruedi, Zhu, Yi, and Guo, Tiannan
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- 2020
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41. Metal–Organic Frameworks with Enhanced Photodynamic Therapy: Synthesis, Erythrocyte Membrane Camouflage, and Aptamer-Targeted Aggregation.
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Zhao, Yuewu, Wang, Jine, Cai, Xue, Ding, Pi, Lv, Haiyin, and Pei, Renjun
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- 2020
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42. Statistical process fault isolation using robust nonnegative garrote.
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Wang, Jian-Guo, Cai, Xue-Zhi, Yao, Yuan, Zhao, Chunhui, Yang, Bang-Hua, Ma, Shi-Wei, and Wang, Sen
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PRODUCTION engineering ,ELECTRONIC data processing ,BRIDGE bearings ,DISCRIMINANT analysis - Abstract
• Multivariate fault isolation methods are proposed based on NNG and R-NNG. • The R-NNG-based method is robust to the outliers in historical process data. • Process variables are arranged according to their responsibility to the fault. • The isolation results are informative for enhancing process understanding. Fault isolation is an essential procedure in multivariate statistical process monitoring, which is used to locate the detected fault. Fault isolation identifies the crucial variables responsible for the detected fault. Accurate isolation results are useful for process engineers in diagnosing the root cause of the fault. Recent studies have revealed the equivalence between the fault isolation task and the variable selection problem in discriminant analysis. Inspired by this idea, a nonnegative garrote-based fault isolation strategy is developed to identify the criticality of each process variable to the detected fault, which is further revised to a more robust version by adopting a robust nonnegative garrote. The critical variables can be identified even when the historical process data are contaminated by outliers using the method proposed in this study. The Tennessee Eastman process was used to illustrate the validity of the proposed method. [ABSTRACT FROM AUTHOR]
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- 2020
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43. High‐throughput proteomic analysis of FFPE tissue samples facilitates tumor stratification.
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Zhu, Yi, Weiss, Tobias, Zhang, Qiushi, Sun, Rui, Wang, Bo, Yi, Xiao, Wu, Zhicheng, Gao, Huanhuan, Cai, Xue, Ruan, Guan, Zhu, Tiansheng, Xu, Chao, Lou, Sai, Yu, Xiaoyan, Gillet, Ludovic, Blattmann, Peter, Saba, Karim, Fankhauser, Christian D., Schmid, Michael B., and Rutishauser, Dorothea
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Formalin‐fixed, paraffin‐embedded (FFPE), biobanked tissue samples offer an invaluable resource for clinical and biomarker research. Here, we developed a pressure cycling technology (PCT)‐SWATH mass spectrometry workflow to analyze FFPE tissue proteomes and applied it to the stratification of prostate cancer (PCa) and diffuse large B‐cell lymphoma (DLBCL) samples. We show that the proteome patterns of FFPE PCa tissue samples and their analogous fresh‐frozen (FF) counterparts have a high degree of similarity and we confirmed multiple proteins consistently regulated in PCa tissues in an independent sample cohort. We further demonstrate temporal stability of proteome patterns from FFPE samples that were stored between 1 and 15 years in a biobank and show a high degree of the proteome pattern similarity between two types of histological regions in small FFPE samples, that is, punched tissue biopsies and thin tissue sections of micrometer thickness, despite the existence of a certain degree of biological variations. Applying the method to two independent DLBCL cohorts, we identified myeloperoxidase, a peroxidase enzyme, as a novel prognostic marker. In summary, this study presents a robust proteomic method to analyze bulk and biopsy FFPE tissues and reports the first systematic comparison of proteome maps generated from FFPE and FF samples. Our data demonstrate the practicality and superiority of FFPE over FF samples for proteome in biomarker discovery. Promising biomarker candidates for PCa and DLBCL have been discovered. [ABSTRACT FROM AUTHOR]
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- 2019
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44. Comment on ‘Prediabetes is an independent risk factor for sarcopenia in older men, but not in older women: the Bunkyo Health Study’ by Kaga et al.
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Qiu, Shanhu, Cai, Xue, Sun, Zilin, and Wu, Tongzhi
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- 2023
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45. PulseDIA: Data-Independent Acquisition Mass Spectrometry Using Multi-Injection Pulsed Gas-Phase Fractionation
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Cai, Xue, Ge, Weigang, Yi, Xiao, Sun, Rui, Zhu, Jiang, Lu, Cong, Sun, Ping, Zhu, Tiansheng, Ruan, Guan, Yuan, Chunhui, Liang, Shuang, Lyu, Mengge, Huang, Shiang, Zhu, Yi, and Guo, Tiannan
- Abstract
The performance of data-independent acquisition (DIA) mass spectrometry (MS) depends on the separation efficiency of peptide precursors. In Orbitrap-based mass spectrometers, separation efficiency of peptide precursors is limited by the relatively slow scanning rate compared to time of flight (TOF)-based MS. Here, we present PulseDIA, a multi-injection gas-phase fractionation (GPF) strategy for enhanced DIA-MS. This is achieved by equally dividing the conventional DIA analysis covering the entire mass range into multiple injections for DIA analyses with complementary windows. Using mouse liver digests, the PulseDIA method identified up to 50% more peptides and 29% more protein groups than that by conventional DIA with the same length of effective gradient time. Compared to conventional multi-injection GPF, PusleDIA exhibited higher flexibility and identified up to 18% more peptides and 8% more protein groups using two injections. The gain of peptides per effective time unit was the highest in PulseDIA compared to conventional DIA and GPF. We further applied the PulseDIA method to profile the proteome of 18 human tissue samples (benign and malignant) from nine cholangiocarcinoma (CCA) patients. PulseDIA identified 7796 protein groups in these CCA samples, with a 14% increase of protein group identification compared to the conventional DIA method. The missing value for protein matrix dropped by 7% using PulseDIA compared to DIA. A total of 681 significantly altered proteins were detected in CCA samples using PulseDIA, including several dysregulated proteins, which were absent in the conventional DIA analysis. Taken together, we present PulseDIA as an enhanced DIA-MS method with improved sensitivity and reproducibility.
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- 2021
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46. Clofazimine broadly inhibits coronaviruses including SARS-CoV-2
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Yuan, Shuofeng, Yin, Xin, Meng, Xiangzhi, Chan, Jasper Fuk-Woo, Ye, Zi-Wei, Riva, Laura, Pache, Lars, Chan, Chris Chun-Yiu, Lai, Pok-Man, Chan, Chris Chung-Sing, Poon, Vincent Kwok-Man, Lee, Andrew Chak-Yiu, Matsunaga, Naoko, Pu, Yuan, Yuen, Chun-Kit, Cao, Jianli, Liang, Ronghui, Tang, Kaiming, Sheng, Li, Du, Yushen, Xu, Wan, Lau, Chit-Ying, Sit, Ko-Yung, Au, Wing-Kuk, Wang, Runming, Zhang, Yu-Yuan, Tang, Yan-Dong, Clausen, Thomas Mandel, Pihl, Jessica, Oh, Juntaek, Sze, Kong-Hung, Zhang, Anna Jinxia, Chu, Hin, Kok, Kin-Hang, Wang, Dong, Cai, Xue-Hui, Esko, Jeffrey D., Hung, Ivan Fan-Ngai, Li, Ronald Adolphus, Chen, Honglin, Sun, Hongzhe, Jin, Dong-Yan, Sun, Ren, Chanda, Sumit K., and Yuen, Kwok-Yung
- Abstract
The COVID-19 pandemic is the third outbreak this century of a zoonotic disease caused by a coronavirus, following the emergence of severe acute respiratory syndrome (SARS) in 20031and Middle East respiratory syndrome (MERS) in 20122. Treatment options for coronaviruses are limited. Here we show that clofazimine—an anti-leprosy drug with a favourable safety profile3—possesses inhibitory activity against several coronaviruses, and can antagonize the replication of SARS-CoV-2 and MERS-CoV in a range of in vitro systems. We found that this molecule, which has been approved by the US Food and Drug Administration, inhibits cell fusion mediated by the viral spike glycoprotein, as well as activity of the viral helicase. Prophylactic or therapeutic administration of clofazimine in a hamster model of SARS-CoV-2 pathogenesis led to reduced viral loads in the lung and viral shedding in faeces, and also alleviated the inflammation associated with viral infection. Combinations of clofazimine and remdesivir exhibited antiviral synergy in vitro and in vivo, and restricted viral shedding from the upper respiratory tract. Clofazimine, which is orally bioavailable and comparatively cheap to manufacture, is an attractive clinical candidate for the treatment of outpatients and—when combined with remdesivir—in therapy for hospitalized patients with COVID-19, particularly in contexts in which costs are an important factor or specialized medical facilities are limited. Our data provide evidence that clofazimine may have a role in the control of the current pandemic of COVID-19 and—possibly more importantly—in dealing with coronavirus diseases that may emerge in the future.
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- 2021
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47. Optimal energy efficiency resource allocation strategy for cognitive clustering network under PUEA attack
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Hu, Linna, Cao, Ning, Shi, Rui, Cai, Xue, Mao, Minghe, and Chen, Zhiyu
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5G has pushed the use of radio spectrum to a new level, and cognitive clustering network can effectively improve the utilization of radio spectrum, which is a feasible way to solve the growing demand for wireless communications. However, cognitive clustering network is vulnerable to PUEA attack, which will lead to the degradation of system detection performance, thereby reducing the energy efficiency. Aiming at these problems, this paper investigates the optimal energy efficiency resource allocation scheme for cognitive clustering network under PUEA attack. A cooperative user selection algorithm based on selection factor is proposed to effectively resist PUEA user attack and improve detection performance. We construct the energy efficiency optimization problem under multi-constraint conditions and transform the nonlinear programming problem into parametric programming problem, which is solved by Lagrangian function and Karush-Kuhn-Tucker condition. Then the sub-gradient iterative algorithm based on optimal energy efficiency under PUEA attack is proposed and its complexity is analyzed. Simulation results indicate that proposed method is effective when subjected to PUEA attacks, and the impact of different parameters on energy efficiency is analyzed.
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- 2020
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48. Accelerated Protein Biomarker Discovery from FFPE Tissue Samples Using Single-Shot, Short Gradient Microflow SWATH MS
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Sun, Rui, Hunter, Christie, Chen, Chen, Ge, Weigang, Morrice, Nick, Liang, Shuang, Zhu, Tiansheng, Yuan, Chunhui, Ruan, Guan, Zhang, Qiushi, Cai, Xue, Yu, Xiaoyan, Chen, Lirong, Dai, Shaozheng, Luan, Zhongzhi, Aebersold, Ruedi, Zhu, Yi, and Guo, Tiannan
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We reported and evaluated a microflow, single-shot, short gradient SWATH MS method intended to accelerate the discovery and verification of protein biomarkers in preclassified clinical specimens. The method uses a 15 min gradient microflow-LC peptide separation, an optimized SWATH MS window configuration, and OpenSWATH software for data analysis. We applied the method to a cohort containing 204 FFPE tissue samples from 58 prostate cancer patients and 10 benign prostatic hyperplasia patients. Altogether we identified 27,975 proteotypic peptides and 4037 SwissProt proteins from these 204 samples. Compared to a reference SWATH method with a 2 h gradient, we found 3800 proteins were quantified by the two methods on two different instruments with relatively high consistency (r= 0.77). The accelerated method consumed only 17% instrument time, while quantifying 80% of proteins compared to the 2 h gradient SWATH. Although the missing value rate increased by 20%, batch effects reduced by 21%. 75 deregulated proteins measured by the accelerated method were selected for further validation. A shortlist of 134 selected peptide precursors from the 75 proteins were analyzed using MRM-HR, and the results exhibited high quantitative consistency with the 15 min SWATH method (r= 0.89) in the same sample set. We further verified the applicability of these 75 proteins in separating benign and malignant tissues (AUC = 0.99) in an independent prostate cancer cohort (n= 154). Altogether, the results showed that the 15 min gradient microflow SWATH accelerated large-scale data acquisition by 6 times, reduced batch effect by 21%, introduced 20% more missing values, and exhibited comparable ability to separate disease groups.
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- 2020
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49. Defect Dynamic Model of the Synergistic Effect in Neutron- and γ-Ray-Irradiated Silicon NPN Transistors
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Song, Yu, Zhou, Hang, Cai, Xue-Fen, Liu, Yang, Yang, Ping, Zhang, Guang-Hui, Zhang, Ying, Lan, Mu, and Wei, Su-Huai
- Abstract
A defect dynamic model is proposed for the positive synergistic effect of neutron- and γ-ray-irradiated silicon NPN transistors. The model considers a γ-ray-induced transformation and annihilation of the neutron-induced divacancy defects in the p-type base region of the transistor. The derived model of the base current predicts a growth function of the γ-ray dose that approaches exponentially an asymptotic value, which depends linearly on the neutron-induced initial displacement damage (DD) and a linear decay function of the dose whose slope depends quadratically on the initial DD. Variable fluence and dose neutron-γ-ray irradiation experiments are carried out, and we find all of the novel dose and fluence dependence predicted by the proposed model are confirmed by the measured data. Our work, hence, identifies that the defect evolution under γ-ray irradiation, rather than the widely believed interface Coulomb interaction, is the dominating mechanism of the synergistic effect. Our work also paves the way for the modification of displacement defects in silicon by γ-ray irradiation.
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- 2020
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50. Antibody responses to SARS-CoV-2 in patients with COVID-19
- Author
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Long, Quan-Xin, Liu, Bai-Zhong, Deng, Hai-Jun, Wu, Gui-Cheng, Deng, Kun, Chen, Yao-Kai, Liao, Pu, Qiu, Jing-Fu, Lin, Yong, Cai, Xue-Fei, Wang, De-Qiang, Hu, Yuan, Ren, Ji-Hua, Tang, Ni, Xu, Yin-Yin, Yu, Li-Hua, Mo, Zhan, Gong, Fang, Zhang, Xiao-Li, Tian, Wen-Guang, Hu, Li, Zhang, Xian-Xiang, Xiang, Jiang-Lin, Du, Hong-Xin, Liu, Hua-Wen, Lang, Chun-Hui, Luo, Xiao-He, Wu, Shao-Bo, Cui, Xiao-Ping, Zhou, Zheng, Zhu, Man-Man, Wang, Jing, Xue, Cheng-Jun, Li, Xiao-Feng, Wang, Li, Li, Zhi-Jie, Wang, Kun, Niu, Chang-Chun, Yang, Qing-Jun, Tang, Xiao-Jun, Zhang, Yong, Liu, Xia-Mao, Li, Jin-Jing, Zhang, De-Chun, Zhang, Fan, Liu, Ping, Yuan, Jun, Li, Qin, Hu, Jie-Li, Chen, Juan, and Huang, Ai-Long
- Abstract
We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT–PCR results and for the identification of asymptomatic infections.
- Published
- 2020
- Full Text
- View/download PDF
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