Publications by authors named "Li Cheng"

2,014 Publications

  • Page 1 of 1

Immunogenicity and safety of a live attenuated varicella vaccine in children 1-12 years of age: A randomized, blinded, controlled, non-inferiority phase 3 clinical trial.

Contemp Clin Trials 2021 Jun 19:106489. Epub 2021 Jun 19.

Institute of Expanded Programme on Immunization, Guizhou Provincial Center for Disease Control and Prevention, Guiyang 550004, Guizhou Province, People's Republic of China. Electronic address:

Objectives: To evaluate the immunogenicity and safety of a live attenuated varicella vaccine produced using a cell factory process.

Methods: In this randomized, blinded, controlled, non-inferiority phase 3 clinical trial conducted in Guizhou, healthy children aged 1-12 years were randomly assigned in a 2: 1 ratio to receive one dose of experimental or control vaccine. Physical examination and first blood collection were performed preimmunization on day 0. Diary cards were collected after day 15. Contact cards and second blood samples were collected on day 30. The primary immunogenicity endpoint was the positive conversion rate of the anti-varicella virus antibody at 30 days postimmunization in susceptible children. Secondary endpoints were the fourfold increase rate, positive conversion rate, geometric mean titer, and geometric mean increase at 30 days after immunization in the total cohort.

Results: Of the 900 children assessed for eligibility, 894 received an experimental or control vaccine. Both the full analysis and safety analysis sets included 894 subjects. The seroconversion rate in the susceptible population was 95.84% in the experimental and 94.76% in the control group. The lower limit of the 95% confidence interval difference was -2.37%, which was greater than the non-inferiority margin set by the program (-10%). No significant difference in solicited adverse reactions was found between the groups. Within 6 months postimmunization, a total of 24 serious adverse events were reported, none related to the studied vaccine.

Conclusion: The live attenuated varicella vaccine produced using a cell factory process was highly immunogenic, safe, and non-inferior to the product in the market. Further studies need to be implemented in the immune persistence, the epidemiological effectiveness and the rare adverse reactions.
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http://dx.doi.org/10.1016/j.cct.2021.106489DOI Listing
June 2021

Innentitelbild: Synthetic Homogeneous Glycoforms of the SARS-CoV-2 Spike Receptor-Binding Domain Reveals Different Binding Profiles of Monoclonal Antibodies (Angew. Chem. 23/2021).

Angew Chem Weinheim Bergstr Ger 2021 Jun 26;133(23):12718. Epub 2021 Apr 26.

Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative Molecules Shanghai Jiao Tong University Shanghai 200240 China.

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http://dx.doi.org/10.1002/ange.202104989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206910PMC
June 2021

Phenotypic and transcriptomic changes in the corneal epithelium following exposure to cigarette smoke.

Environ Pollut 2021 Jun 12;287:117540. Epub 2021 Jun 12.

Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, Xiamen, 361102, China. Electronic address:

Cigarette smoke extract (CSE), a complex mixture of compounds, contributes to a range of eye diseases; however, the underlying pathophysiological responses to tobacco smoke remain ambiguous. The purpose of the present study was to evaluate the cigarette smoke-induced phenotypic and transcriptomic changes in the corneal epithelium with a view to elucidating the likely underlying mechanism. Accordingly, for the first time, we characterized the genome-wide effects of CSE on the corneal epithelium. The ocular surface of the mice in the experimental groups was exposed to CSE for 1 h per day for a period of one week, while mice in the control group were exposed to preservative-free artificial tears. Corneal fluorescein staining, in vivo confocal microscopy and scanning electron microscopy were performed to examine the corneal ultrastructure. Transcriptome sequencing and bioinformatics analysis were performed followed by RT-qPCR to validate gene expression changes. The results indicate that CSE exposure disrupted the structural integrity of the superficial epithelium, decreased the density of microvilli, and compromised the corneal epithelial barrier intactness. RNA-seq revealed 667 differentially expressed genes, and functional analysis highlighted the enhancement of several biological processes such as antioxidant activity and the response to oxidative stress. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that glutathione metabolism and drug metabolism cytochrome P450 were the most relevant pathways contributing to the effects of CSE on the corneal epithelium. Protein-protein interaction (PPI) network analysis illustrated that GCLC, NQO1, and HMOX1 were the most relevant nodes. In conclusion, the present study indicates that CSE exposure induces changes in the phenotype and genotype of the corneal epithelium. The antioxidant response element is essential for counteracting the effects of cigarette smoke on this tissue layer. These results shed novel insights into how cigarette smoke damages this ocular surface.
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http://dx.doi.org/10.1016/j.envpol.2021.117540DOI Listing
June 2021

Chronic Jet Lag Exacerbates Jejunal and Colonic Microenvironment in Mice.

Front Cell Infect Microbiol 2021 1;11:648175. Epub 2021 Jun 1.

Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Institute of Digestive Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Evidence suggests that circadian rhythm disorder is associated with a variety of gastrointestinal diseases, and the circadian rhythm plays a key role in maintaining the homeostasis of intestinal flora. The underlying mechanisms are still not completely identified. This study was aimed to explore whether jet lag-caused circadian disruption influences gut microbiome and its metabolites.

Methods: Mice were synchronized with 12-h light/dark cycles (control group) or subjected to daily 8-h advance of the light/dark cycle for every 3 days (jet-lagged group). Four months later, fecal samples and jejunal contents were collected and analyzed by 16S rRNA gene sequencing. In addition, fecal samples were subjected to metabolome analysis with ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS).

Results: The results of 16s rRNA sequencing showed that chronic jet lag led to decreased microbial abundance, richness, and diversity in both feces and jejunal contents. ANOSIM analysis revealed significant difference between control and jet-lagged groups. As the colonic microbiome, the abundance of Bacteroidetes phylum was significantly decreased and that of Actinobacteria phylum was increased in jet-lagged mice. Jet lag increased the ratio of Firmicutes to Bacteroidetes, an indicator for the imbalance of gut microbiota. Metabolome analysis of fecal samples showed that the levels of tryptophan and its derivatives were decreased in jet-lagged mice. In addition, fecal levels of secondary bile acids changed under jet lag conditions. Correlation analysis identified associations between tryptophan (and its derivatives) levels and colonic microbiota.

Conclusions: This study presents a comprehensive landscape of gut microbiota and its metabolites in mice subjected to chronic jet lag. The results suggest that circadian disruption may lead to changes in fecal and jejunal microbiota and fecal metabolites. Moreover, our results demonstrate a novel interplay between the gut microbiome and metabolome.
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http://dx.doi.org/10.3389/fcimb.2021.648175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204051PMC
June 2021

Myocardial infarction detected by a smartwatch after transcatheter aortic valve replacement during the COVID-19 pandemic.

World J Emerg Med 2021 ;12(3):247-248

Department of Cardiology, the Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310009, China.

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http://dx.doi.org/10.5847/wjem.j.1920-8642.2021.03.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188292PMC
January 2021

An Efficient Trap Passivator for Perovskite Solar Cells: Poly(propylene glycol) bis(2-aminopropyl ether).

Nanomicro Lett 2020 Aug 29;12(1):177. Epub 2020 Aug 29.

CAS Key Laboratory of Organic Solids, Beijing National Laboratory for Molecular Sciences, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, People's Republic of China.

Perovskite solar cells (PSCs) are regarded as promising candidates for future renewable energy production. High-density defects in the perovskite films, however, lead to unsatisfactory device performances. Here, poly(propylene glycol) bis(2-aminopropyl ether) (PEA) additive is utilized to passivate the trap states in perovskite. The PEA molecules chemically interact with lead ions in perovskite, considerably passivate surface and bulk defects, which is in favor of charge transfer and extraction. Furthermore, the PEA additive can efficiently block moisture and oxygen to prolong the device lifetime. As a result, PEA-treated MAPbI (MA: CHNH) solar cells show increased power conversion efficiency (PCE) (from 17.18 to 18.87%) and good long-term stability. When PEA is introduced to (FAPbI)(MAPbBr) (FA: HC(NH)) solar cells, the PCE is enhanced from 19.66 to 21.60%. For both perovskites, their severe device hysteresis is efficiently relieved by PEA.
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http://dx.doi.org/10.1007/s40820-020-00517-yDOI Listing
August 2020

Molecular simulation of nano polyhedral oligomeric silsesquioxane doping effect on the properties of two-component crosslinked epoxy resin.

J Mol Graph Model 2021 Jun 7;107:107961. Epub 2021 Jun 7.

State Key Laboratory of Power Transmission Equipment & System Security and New Technology, Chongqing University, Chongqing, China.

Epoxy resin (EP) has been extensively used in the field of insulation for its excellent electrical strength, mechanical property, chemical stability, and low cost. In this paper, computer molecular simulation is used to analyze the influence of nano-POSS (Nano-Polyhedral Oligomericsils Esquioxane) doping on the properties of epoxy composite from the micro point of view, which can provide a scientific basis for the optimization of the epoxy system. Two kinds of nano-POSS fillers with different mass fractions were doped into the base material of diglycidyl ether of bisphenol A (DGEBA) and 3,4-epoxycyclohexylmethyl 3,4-epoxycyclohexanecar (OSC). By molecular dynamics (MD) simulation the influence of nanofillers on the microstructure, thermal and mechanical properties of the composite were analyzed. Simulation results show that the doping of nano-POSS can improve the thermal and mechanical properties of the epoxy composite. Different nano-POSS has little effect on the glass transition temperature (T), coefficient of thermal expansion (CTE), and mechanical properties of the epoxy system, while the filling amount has an obvious improvement effect. Compared with EP/methyl-POSS system, the thermal and mechanical properties of the EP/phenyl-POSS system are better. At the same time, the doping of nano-POSS changed the microstructure parameters of epoxy composite. With the increase of nano-POSS filler content, fractional free volume (FFV) and mean square displacement (MSD) of both EP/POSS systems increased after the first drop. Besides, when the content of nano-POSS exceeded a certain range, the aggregation of filler itself hindered the accumulation of epoxy molecular chain segments.
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http://dx.doi.org/10.1016/j.jmgm.2021.107961DOI Listing
June 2021

New insights into the alleviating role of starch derivatives on dough quality deterioration caused by freeze.

Food Chem 2021 May 28;362:130240. Epub 2021 May 28.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; Collaborative Innovation Center of Food Safety and Quality Control, Jiangnan University, Wuxi 214122, China. Electronic address:

The alleviating role of starch derivatives on the quality deterioration of frozen steamed bread dough was investigated in terms of derivative structure, the bread characteristics and dough properties including freezable water contents, yeast activity as well as dough viscoelasticity. The addition of starch derivatives including short-clustered maltodextrin (SCMD), DE2 maltodextrin (MD) and pregelatinized starch (PGS) significantly increased the specific volume and decreased the hardness of steamed bread compared with Control bread after 8-week frozen storage. Lower freezable water content was found in PGS dough than SCMD dough, which was consistent with the results of water absorption index of starch derivatives. The analysis of dough gassing rate and yeast survival ratio demonstrated SCMD could provide more cryoprotection for yeast cells. Meanwhile, a higher elastic module and a more continuous gluten-network structure of SCMD dough were found after 8-week frozen storage. These results indicated starch derivatives especially SCMD were promising to be used as the alternative improvers in frozen dough production.
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http://dx.doi.org/10.1016/j.foodchem.2021.130240DOI Listing
May 2021

Effects of different doses of cisatracurium on intraoperative nerve monitoring in thyroid surgery: a randomised controlled trial.

Br J Anaesth 2021 Jun 9. Epub 2021 Jun 9.

Department of Anaesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai, China; Translational Research Institute of Brain and Brain-like Intelligence, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Anaesthesiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address:

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http://dx.doi.org/10.1016/j.bja.2021.05.011DOI Listing
June 2021

Preparation and characterization of octenyl succinic anhydride modified waxy maize starch hydrolyzate/chitosan complexes with enhanced interfacial properties.

Carbohydr Polym 2021 Sep 20;267:118228. Epub 2021 May 20.

Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, Wuxi 214122, Jiangsu Province, PR China; School of Food Science and Technology, Jiangnan University, 1800 LiHu Avenue, Wuxi 214122, Jiangsu Province, PR China; Collaborative Innovation Center for Food Safety and Quality Control, Jiangnan University, 1800 LiHu Avenue, Wuxi 214122, Jiangsu Province, PR China. Electronic address:

The preparation and characterization of colloidal complexes based on octenyl succinic anhydride starch hydrolyzate (OSAS) and chitosan (CS) were conducted. Results showed that OSA-S/CS ratio (r) and pH significantly affected complex turbidities and yields. The highest turbidity and yield were obtained at r = 6:1 when pH was fixed, and at pH 6.5 when r was fixed. All complexes remained liquid-like except that formed at pH 6.5, which exhibited a gel structure due to the strongest complexation. OSA-S/CS complexes had intertwined core-shell microstructure and exhibited electrostatic interactions between COO and NH groups of OSA-S and CS, respectively. The complexes prepared at r = 6:1 and pH 6.0 exhibited the most suitable wettability (θ = 91.97°) and interfacial adsorption dynamics. The compact lamellar network and intact cores of these complexes were also shown. This work provides profound and comprehensive information about the formation and physicochemical properties of OSA-S/CS complexes.
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http://dx.doi.org/10.1016/j.carbpol.2021.118228DOI Listing
September 2021

Integrative Analysis of Genome, 3D Genome, and Transcriptome Alterations of Clinical Lung Cancer Samples.

Genomics Proteomics Bioinformatics 2021 Jun 8. Epub 2021 Jun 8.

Center for Bioinformatics, School of Life Sciences, Center for Statistical Science, Peking University, Beijing 100871, China. Electronic address:

Genomic studies of cancer cell alterations, such as mutations, copy number variations (CNVs), and translocations, greatly promote our understanding of the genesis and development of cancer. However, the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical difficulties. To explore the 3D genome structure in clinical lung cancer, we performed Hi-C experiments using paired normal and tumor cells harvested from patients with lung cancer, combining with RNA-seq analysis. We demonstrated the feasibility of studying 3D genome of clinical lung cancer samples with a small number of cells (1 × 10), compared the genome architecture between clinical samples and cell lines of lung cancer, and identified conserved and changed spatial chromatin structures between normal and cancer samples. We also showed that Hi-C data can be used to infer CNVs and point mutations in cancer. By integrating those different types of cancer alterations, we showed significant associations between CNVs, 3D genome, and gene expression. We propose that 3D genome mediates the effects of cancer genomic alterations on gene expression through altering regulatory chromatin structures. Our study highlights the importance of analyzing 3D genomes of clinical cancer samples in addition to cancer cell lines and provides an integrative genomic analysis pipeline for future larger-scale studies in lung cancer and other cancers.
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http://dx.doi.org/10.1016/j.gpb.2020.05.007DOI Listing
June 2021

Leached starch content and molecular size during sorghum steaming for baijiu production is not determined by starch fine molecular structures.

Int J Biol Macromol 2021 Jun 9;184:50-56. Epub 2021 Jun 9.

School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Institutes of Agricultural Science and Technology Development of Yangzhou University, Yangzhou 225009, Jiangsu, China. Electronic address:

Sorghum steaming properties are important for both flavor and brewing efficiency of baijiu (Chinese alcohol liquor). However, it is currently unclear with respects to structural factors that affect sorghum steaming properties during baijiu production. In this study, starch fine molecular structures were characterized by size-exclusion chromatography and fluorophore-assisted carbohydrate electrophoresis for 8 sorghum varieties used in baijiu production. Starch crystalline structures and ordering of double helices were characterized by the X-ray diffraction and differential scanning calorimetry. Results showed that only small differences were observed for starch molecular size distributions and chain-length distributions in the raw sorghum flour. Of significance, the leached starch content and molecular size during steaming was very different among these sorghum varieties. Furthermore, Spearman correlation analysis showed that there was no significant correlation between starch fine structural parameters with the leached starch content. On the other hand, the correlation analysis showed that leached starch molecular size was negatively correlated with starch crystallinity, while positively correlated with the onset and peak gelatinization temperatures. It is concluded that the sorghum steaming property is controlled by the starch crystalline structures instead of starch fine molecular structures. These results could help the baijiu industry to produce baijiu with more desirable properties.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.031DOI Listing
June 2021

Application of first-order kinetics modeling to reveal the nature of starch digestion characteristics.

Food Funct 2021 Jun 11. Epub 2021 Jun 11.

School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China. and Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Institutes of Agricultural Science and Technology Development of Yangzhou University, Yangzhou 225009, Jiangsu, China.

Mathematical modeling of in vitro starch digestograms is essential to understand starch structure-digestibility relationships as it covers all detailed information of the starch digestograms with only a few kinetics-based parameters. However, many assumptions exist for these mathematical models, which are frequently overlooked by researchers and lead to inappropriate or even wrong interpretations of the fitted parameters. This review presents a critical evaluation of four mostly applied empirical first-order kinetics models including single first-order kinetics (SK), logarithm of slope (LOS) transformed kinetics, parallel first-order kinetics (PK) and the combination of parallel and sequential (CPS) kinetics models. For homogeneous food systems, the SK model is perfectly suitable, whereas the LOS, PK and CPS models were suitably developed for food systems containing multiple digestible fractions. For the digestion of starch containing multiple digestible fractions, the LOS model assumed a sequential digestion pattern, whereas the PK model assumed a parallel pattern. In the current review, there is also emphasis on the recently developed CPS model, which is able to differentiate the sequential and parallel digestion patterns for different starch digestible fractions existing in food systems. Understanding these assumptions enables a better selection of an appropriate mathematical model for improving the understanding of in vitro starch digestion characteristics. This review meets the growing interest of the food industry in terms of developing a new generation of foods with slower starch digestibility.
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http://dx.doi.org/10.1039/d1fo00450fDOI Listing
June 2021

Detection of alkanolamines in liquid cement grinding aids by HPLC coupled with evaporative light scattering detector.

Turk J Chem 2021 28;45(2):430-435. Epub 2021 Apr 28.

Department of Health Inspection and Quarantine Technology, Faculty of Medical Technology, Ningbo College of Health Science, Ningbo China.

Triethanolamine (TEA), triisopropanolamine (TIPA), diethanol isopropanolamine (DEIPA) are necessary cement additives, and knowing their contents is needed for quality control and also to understand final properties of the cement. Whether it is the production of grinding aids, technical research and development or application research all involve the detection of grinding aids. This work developed a simple analytical technique for the simultaneous analysis of these alkanolamines in liquid cement grinding aids using high-performance liquid chromatography (HPLC) combined with evaporative light scattering detection (ELSD). HPLC was conducted by an XBridge C18 column (with dimensions 4.6 × 250 mm and 5 µm particles) using methanol and 0.1% trichloroacetic acid as mobile elution phases. The ELSD sprayer and drift tube temperatures were 60 ºC and 90 ºC, respectively. HPLC-ELSD developed in this work demonstrated 1) high sensitivity with limits of detection for the three analytes are 0.15, 0.54, 1.04 µg/mL; 2) good linearity with correlation coefficients equal to 0.997-0.999 over the tested concentration range; 3) excellent repeatability with intra- and interday coefficient of variation (CV) below 2.71% and 4, satisfactory accuracy with recovery in the 95.5%-100.8% range. This novel method is a powerful, time- and costeffective tool for alkanolamine analyses and quality control.
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http://dx.doi.org/10.3906/kim-2007-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164192PMC
April 2021

Evaluation of Renal Tissue Oxygenation Using Blood Oxygen Level-Dependent Magnetic Resonance Imaging in Chronic Kidney Disease.

Kidney Blood Press Res 2021 Jun 4:1-11. Epub 2021 Jun 4.

Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.

Background: Blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) has been widely used to assess renal oxygenation changes in different kidney diseases in recent years. This study was designed to evaluate and compare renal tissue oxygenation using 2 BOLD-MRI analysis methods, namely, the regional and whole-kidney region of interest (ROI) selection methods.

Methods: The study ended up with 10 healthy controls and 40 chronic kidney disease (CKD) patients without dialysis. Their renal BOLD-MRI data were analyzed using whole-kidney ROI selection method and compared with regional ROI selection method.

Results: We found the cortical, medullary, and whole-kidney R2* values were significantly higher in CKD patients than those in controls. Compared with the regional ROI selection method, the whole-kidney ROI selection method yielded higher cortical R2* values in both controls and CKD patients. The whole-kidney R2* values of deteriorating renal function group were significantly higher than those in stable renal function group.

Conclusions: Cortical and medullary oxygenation was decreased significantly in CKD patients compared with the healthy controls, particularly in the medulla. The whole-kidney R2* values were positively correlated with kidney function and inversely correlated with the estimated glomerular filtration rate and effective renal plasma flow. Whole-Kidney R2* value might effectively predict the progression of renal function in patients with CKD.
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http://dx.doi.org/10.1159/000515709DOI Listing
June 2021

Gankyrin activates the hedgehog signalling to drive metastasis in osteosarcoma.

J Cell Mol Med 2021 Jun 5. Epub 2021 Jun 5.

Department of Orthopaedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.

Gankyrin is a regulatory subunit of the 26-kD proteasome complex and promotes the occurrence and progression of many malignancies. However, the role of gankyrin in osteosarcoma (OS) metastasis remains unclear. Hedgehog signalling has been shown to regulate stem cell homeostasis and cancer metastasis, but the mechanisms that activate this pathway in OS are still poorly understood. Here, a series of in vitro and in vivo assays were carried out to explore the function and mechanism of gankyrin regulating Hedgehog signalling in OS. We demonstrated that gankyrin promotes migration, invasion and regulates the expression of some stemness factors by up-regulating Gli1 in OS. Importantly, our data showed an interaction between gankyrin and Gli1. Moreover, gankyrin suppresses the ubiquitin-mediated degradation of Gli1 protein in OS. Gankyrin also significantly promotes the lung metastasis of OS in vivo. Our findings suggest that gankyrin drives metastasis and regulates the expression of some stemness factors in osteosarcoma by activating Hedgehog signalling, indicating that drug screening for compounds targeting gankyrin may contribute to the development of novel and effective therapies for OS.
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http://dx.doi.org/10.1111/jcmm.16576DOI Listing
June 2021

PI3K/AKT pathway mediates the antidepressant- and anxiolytic-like roles of hydrogen sulfide in streptozotocin-induced diabetic rats via promoting hippocampal neurogenesis.

Neurotoxicology 2021 Jun 1;85:201-208. Epub 2021 Jun 1.

Hengyang Key Laboratory of Neurodegeneration and Cognitive Impairment, Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang, 421001, Hunan, PR China; Institute of Neurology, The First Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, PR China. Electronic address:

We have previously demonstrated that hydrogen sulfide (HS), the third endogenous gasotransmitter, ameliorates the depression- and anxiety-like behaviors in diabetic rats, but the underlying mechanism remains unclear. The present was aimed to investigate whether the hippocampal phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway mediates HS-ameliorated depression- and anxiety-like behaviors in diabetic rats by improving the hippocampal neurogenesis. The depression-like behaviors were examined by Tail suspension test (TST), the anxiety-like behaviors were examined by Elevated plus maze test (EPM), and the locomotor activity was detected by Open Field Test (OFT). The expressions of doublecortin (DCX), neuron-specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), p-AKT, and AKT in the hippocampus were determined by Western blot analysis. Results showed that NaHS, a donor of exogenous HS, not only activated the hippocampal PI3K/AKT pathway, as evidenced by the increase of phosphorylated AKT, but also favorably reversed streptozotocin (STZ)-disturbed hippocampal neurogenesis, as evidenced by the increases in the expressions of DCX and NeuN as well as the decrease in the expression of GFAP in the hippocampus of STZ-induced diabetic rats. Furthermore, inhibited PI3K/AKT pathway by LY294002 significantly abolished HS-exerted the improvement of hippocampal neurogenesis and the antidepressant- and anxiolytic-like effects in the STZ-induced diabetic rats. Taken together, these results uncover that the activation of hippocampal PI3K/AKT pathway plays an important role to restore hippocampal neurogenesis and subsequently to mediate the antidepressant- and anxiolytic-like roles of HS in STZ-induced diabetic rats and enhance our understanding of the robustness of HS as a therapeutic strategy for treatment of depression in diabetes mellitus.
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http://dx.doi.org/10.1016/j.neuro.2021.05.016DOI Listing
June 2021

Metabolomics reveals a correlation between hydroxyeicosatetraenoic acids and allergic asthma: Evidence from three years' immunotherapy.

Pediatr Allergy Immunol 2021 Jun 4. Epub 2021 Jun 4.

State Key Laboratory for Quality Research in Chinese Medicines, Macau University of Science and Technology, Macao, China.

Background: Subcutaneous immunotherapy (SCIT) is an effective, safe, preventative treatment for allergic asthma; however, potential biomarkers for monitoring SCIT have rarely been reported.

Objective: Metabolomics was utilized for the discovery of new biomarkers and analyzing disease pathophysiology of allergic asthma, and it was also applied to determine the metabolomic profiles of serum samples from children with asthma undergoing SCIT and identify potential biomarkers for allergic asthma and its therapeutic monitoring.

Methods: Untargeted metabolomics using ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry was performed on 15 asthmatic and 15 healthy pediatric sera to profile carboxylic acids. Statistical analysis combined with pathway enrichment analysis was applied to identify potential biomarkers. Then, targeted metabolomics was performed to study longitudinal changes of eicosanoid profiles on sera from 20 participants with asthma who received SCIT at baseline, 6 months, one, two, and three years (ChiCTR-DDT-13003728).

Results: Metabolomic analysis revealed that levels of eicosanoids, particularly 12(S)-hydroxyeicosatetraenoic acid (HETE; AUC = 0.94, p < .0001) and 15(S)-HETE (AUC = 0.89, p = .0028), metabolized from arachidonic acid by lipoxygenase and glutathione peroxidase enzymes, were significantly higher in asthma group than in healthy individuals. Furthermore, levels of these important metabolites increased in the first year of SCIT treatment and then decreased from years one to three, being significantly lower after three years of treatment than baseline levels.

Conclusion: 12(S)- and 15(S)-HETEs are potential biomarkers to participate in the pathogenesis and treatment of allergic asthma. Moreover, these metabolites may be a new target for biological indicators to monitor the therapeutic effect of SCIT, particularly in the setting of allergic asthma.
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http://dx.doi.org/10.1111/pai.13569DOI Listing
June 2021

Clinical Characteristics of Foreign-Imported COVID-19 Cases in Xi'an, China.

Int J Gen Med 2021 25;14:2069-2078. Epub 2021 May 25.

Xi'an Public Health Center, Xi'an, Shaanxi, 710200, People's Republic of China.

Background: Effective management of foreign-imported COVID-19 cases is a new and great challenge for China. Our study focused on the foreign-imported COVID-19 cases to provide detailed data for insights into the prevention, early diagnosis, treatment and control of imported COVID-19.

Methods: For this observational and retrospective study, we investigated the clinical characteristics of imported COVID-19 cases that were confirmed by real-time RT-PCR in the Xi'an Public Health Center from 29 March 2020 to 31 August 2020.

Results: Of the 79 patients with COVID-19, 19 (24.1%) had exposure to confirmed COVID-19 patients, 15 (19.0%) had exposure to suspicious COVID-19 patients, and 45 (56.9%) had an unclear history of exposure to confirmed patients. The mean age of the patients was 38 years, and 70 (88.7%) patients were male. Except for 2 severe cases, the remaining 58 (73.4%) cases displayed mild or moderate symptoms, and 19 (24.2%) infected patients were asymptomatic. Twenty-one (26.6%) patients were not diagnosed until a third or later nucleic acid test. Ten (12.7%) patients had chronic diseases. The most common manifestations of the patients were cough [18 (22.8%) cases], fever [9 (11.4%) cases] and sore throat [9 (11.4%) cases]. Forty-one (51.9%) cases showed abnormal chest CT images, To date, all patients have been discharged, and no patient has died.

Conclusion: The imported COVID-19 cases in Xi'an were mainly young and middle-aged adults with mild or moderate symptoms who had a low rate of comorbidity, showed favourable laboratory and chest CT images, and had a better prognosis. Notably, for suspected COVID-19 cases, at least three consecutive nucleic acid tests should be carried out to avoid missed detection of infected patients. Except for severe cases, high-level medical resources are not necessary in most cases.
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http://dx.doi.org/10.2147/IJGM.S315159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164692PMC
May 2021

Malnutrition in Relation with Dietary, Geographical, and Socioeconomic Factors among Older Chinese.

Biomed Environ Sci 2021 May;34(5):337-347

National Institute of Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.

Objective: Nutrition is closely related to the health of the elderly population. This study aimed to provide a comprehensive picture of the nutrition status of elderly Chinese and its related dietary, geographical, and socioeconomic factors.

Methods: A total of 13,987 ≥ 60-year-old persons from the 2010-2013 Chinese National Nutrition and Health Survey were included to evaluate various aspects of malnutrition, including underweight, overweight or obesity, and micronutrient inadequacy.

Results: Overall, the prevalence of obesity, overweight, and underweight was 12.4%, 34.8%, and 5.7%, respectively, with disparities both geographically and socioeconomically. The prevalence of underweight was higher among the older old (≥ 75 years), rural residents and those with low income, with low education status, and residing in undeveloped West areas. More than 75% of the elderly do not meet the Dietary Reference Intakes for vitamins A, B , B , and E, folate, calcium, selenium, potassium, biotin, and choline, with the prevalence of inadequate intake increasing with age for most nutrients. At the population level, the mean intakes of numerous food groups did not meet the recommendations by the Chinese Dietary Guideline.

Conclusions: Obesity epidemic, inadequacy of micronutrient intake, and high prevalence of underweight and anemia in susceptible older people are the major nutrition challenges for the rapidly aging population in China.
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http://dx.doi.org/10.3967/bes2021.045DOI Listing
May 2021

Comparison of the major cell populations among osteoarthritis, Kashin-Beck disease and healthy chondrocytes by single-cell RNA-seq analysis.

Cell Death Dis 2021 May 27;12(6):551. Epub 2021 May 27.

School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, 710061, Xi'an, Shaanxi, P. R. China.

Chondrocytes are the key target cells of the cartilage degeneration that occurs in Kashin-Beck disease (KBD) and osteoarthritis (OA). However, the heterogeneity of articular cartilage cell types present in KBD and OA patients and healthy controls is still unknown, which has prevented the study of the pathophysiology of the mechanisms underlying the roles of different populations of chondrocytes in the processes leading to KBD and OA. Here, we aimed to identify the transcriptional programmes and all major cell populations in patients with KBD, patients with OA and healthy controls to identify the markers that discriminate among chondrocytes in these three groups. Single-cell RNA sequencing was performed to identify chondrocyte populations and their gene signatures in KBD, OA and healthy cells to investigate their differences as related to the pathogenetic mechanisms of these two osteochondral diseases. We performed immunohistochemistry and quantitative reverse-transcription PCR (qRT-PCR) assays to validate the markers for chondrocyte population. Ten clusters were labelled by cell type according to the expression of previously described markers, and one novel population was identified according to the expression of a new set of markers. The homeostatic and mitochondrial chondrocyte populations, which were identified by the expression of the unknown markers MT1X and MT2A and MT-ND1 and MT-ATP6, were markedly expanded in KBD. The regulatory chondrocyte population, identified by the expression of CHI3L1, was markedly expanded in OA. Our study allows us to better understand the heterogeneity of chondrocytes in KBD and OA and provides new evidence of differences in the pathogenetic mechanisms between these two diseases.
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http://dx.doi.org/10.1038/s41419-021-03832-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160352PMC
May 2021

Bioinformatic analysis of differentially expressed genes as prognostic markers in pheochromocytoma and paraganglioma tumors.

Genes Genet Syst 2021 May 26. Epub 2021 May 26.

Department of Hand and Microsurgery, Xiangya Hospital, Central South University.

The pathogenesis of pheochromocytoma and paraganglioma (PCPG) catecholamine-producing tumors is exceedingly complicated. Here, we sought to identify important genes affecting the prognosis and survival rate of patients suffering from PCPG. We analyzed 95 samples obtained from two microarray data series, GSE19422 and GSE60459, from the Gene Expression Omnibus (GEO) repository. First, differentially expressed genes (DEGs) were identified by comparing 87 PCPG tumor samples and eight normal adrenal tissue samples using R language. The GEO2R tool and Venn diagram software were applied to the Database for Annotation, Visualization and Integrated Discovery (DAVID) to analyze Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO). We further employed Cytoscape with the Molecular Complex Detection (MCODE) tool to make protein-protein interactions visible for the Search Tool for Retrieval of Interacting Genes (STRING). These procedures resulted in 30 candidate DEGs, which were subjected to Kaplan-Meier analysis and validated by Gene Expression Profiling Interactive Analysis (GEPIA) to determine their influence on overall survival rate. Finally, we identified ALDH3A2 and AKR1B1, two genes in the glycerolipid metabolism pathway, as being particularly enriched in PCPG tumors and correlated with T and B tumor-infiltrating immune cells. Our results suggest that these two DEGs are closely associated with the prognosis of malignant PCPG tumors.
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http://dx.doi.org/10.1266/ggs.20-00057DOI Listing
May 2021

Phase separation of OCT4 controls TAD reorganization to promote cell fate transitions.

Cell Stem Cell 2021 May 20. Epub 2021 May 20.

RNA Biomedical Institute, Sun Yat-Sen Memorial Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, China; Department of Cell Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China. Electronic address:

Topological-associated domains (TADs) are thought to be relatively stable across cell types, although some TAD reorganization has been observed during cellular differentiation. However, little is known about the mechanisms through which TAD reorganization affects cell fate or how master transcription factors affect TAD structures during cell fate transitions. Here, we show extensive TAD reorganization during somatic cell reprogramming, which is correlated with gene transcription and changes in cellular identity. Manipulating TAD reorganization promotes reprogramming, and the dynamics of concentrated chromatin loops in OCT4 phase separated condensates contribute to TAD reorganization. Disrupting OCT4 phase separation attenuates TAD reorganization and reprogramming, which can be rescued by fusing an intrinsically disordered region (IDR) to OCT4. We developed an approach termed TAD reorganization-based multiomics analysis (TADMAN), which identified reprogramming regulators. Together, these findings elucidate a role and mechanism of TAD reorganization, regulated by OCT4 phase separation, in cellular reprogramming.
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http://dx.doi.org/10.1016/j.stem.2021.04.023DOI Listing
May 2021

Ultrastable Glassy Polymer Films with an Ultradense Brush Morphology.

ACS Nano 2021 Jun 25;15(6):9568-9576. Epub 2021 May 25.

Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544, United States.

Glassy polymer films with extreme stability could enable major advancements in a range of fields that require the use of polymers in confined environments. Yet, from a materials design perspective, we now know that the glass transition temperature () and thermal expansion of polymer thin films can be dramatically different from those characteristics of the bulk, , exhibiting confinement-induced diminished thermal stability. Here, we demonstrate that polymer brushes with an ultrahigh grafting density, , an ultradense brush morphology, exhibit a significant enhancement in thermal stability, as manifested by an exceptionally high and low expansivity. For instance, a 5 nm thick polystyrene brush film exhibits an ∼75 K increase in and ∼90% reduction in expansivity compared to a spin-cast film of similar thickness. Our results establish how morphology can overcome confinement and interfacial effects in controlling thin-film material properties and how this can be achieved by the dense packing and molecular ordering in the amorphous state of ultradense brushes prepared by surface-initiated atom transfer radical polymerization in combination with a self-assembled monolayer of initiators.
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http://dx.doi.org/10.1021/acsnano.0c09631DOI Listing
June 2021

Chemically defined and xeno-free culture condition for human extended pluripotent stem cells.

Nat Commun 2021 05 21;12(1):3017. Epub 2021 May 21.

Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.

Extended pluripotent stem (EPS) cells have shown great applicative potentials in generating synthetic embryos, directed differentiation and disease modeling. However, the lack of a xeno-free culture condition has significantly limited their applications. Here, we report a chemically defined and xeno-free culture system for culturing and deriving human EPS cells in vitro. Xeno-free human EPS cells can be long-term and genetically stably maintained in vitro, as well as preserve their embryonic and extraembryonic developmental potentials. Furthermore, the xeno-free culturing system also permits efficient derivation of human EPS cells from human fibroblast through reprogramming. Our study could have broad utility in future applications of human EPS cells in biomedicine.
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http://dx.doi.org/10.1038/s41467-021-23320-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139978PMC
May 2021

Influence of Surface Texture on the Variation of Electrokinetic Streaming Potentials.

Langmuir 2021 Jun 21;37(22):6736-6743. Epub 2021 May 21.

Department of Mechanical Engineering, Michigan State University, East Lansing, Michigan 48824, United States.

The electrokinetic streaming potential () obtained through electrolyte flow in a microchannel is shown to be related to the underlying surface pattern. Pillar, mesh, and groove patterns were studied for comparing the relative magnitudes of the with air-/liquid-filled surfaces. A record value of the related figure of merit, in terms of the developed per-unit applied pressure, of ∼0.127 mV/Pa, was observed in a mesh texture liquid-filled surface (LFS) impregnated with an electrolyte-immiscible oil. The study indicated that increasing the solid fraction of the pattern surface decreases the effective slip length while enhancing the overall channel ζ potential. Consequently, maximizing the obtained implies a balancing of the slip with the surface potential, with plausibly more significance of the latter. The work has implications for higher-efficiency electrical voltage sources.
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http://dx.doi.org/10.1021/acs.langmuir.1c00738DOI Listing
June 2021

Comparing Symptomatic and Asymptomatic Carotid Artery Atherosclerosis in Patients With Bilateral Carotid Vulnerable Plaques Using Magnetic Resonance Imaging.

Angiology 2021 May 21:33197211012531. Epub 2021 May 21.

Center for Biomedical Imaging Research, Department of Biomedical Engineering, 118223Tsinghua University School of Medicine, Beijing, China.

We compared plaque characteristics between symptomatic and asymptomatic sides in patients with bilateral carotid vulnerable plaques using magnetic resonance imaging (MRI). Participants (n = 67; mean age: 65.8 ± 7.7 years, 61 males) with bilateral carotid vulnerable plaques were included. Vulnerable plaques were characterized by intraplaque hemorrhage (IPH), large lipid-rich necrotic core (LRNC), or fibrous cap rupture (FCR) on MRI. Symptomatic vulnerable plaques showed greater plaque burden, LRNC volume (median: 221.4 vs 134.8 mm, = .003), IPH volume (median: 32.2 vs 22.5 mm, = .030), maximum percentage (Max%) LRNC (median: 51.3% vs 41.8%, = .002), Max%IPH (median: 13.4% vs 9.5%, = .022), cumulative slices of LRNC (median: 10 vs 8, = .005), and more juxtaluminal IPH and/or thrombus (29.9% vs 6.0%, = .001) and FCR (37.3% vs 16.4%, = .007) than asymptomatic ones. After adjusting for plaque burden, differences in juxtaluminal IPH and/or thrombus (odds ratio [OR]: 5.49, 95% CI: 1.61-18.75, = .007) and FCR (OR: 2.90, 95% CI: 1.16-7.24, = .022) between bilateral sides remained statistically significant. For patients with bilateral carotid vulnerable plaques, symptomatic plaques had greater burden, more juxtaluminal IPH and/or thrombus, and FCR compared with asymptomatic ones. The differences in juxtaluminal IPH and/or thrombus and FCR between bilateral sides were independent of plaque burden.
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http://dx.doi.org/10.1177/00033197211012531DOI Listing
May 2021

Ultrahigh-energy photons up to 1.4 petaelectronvolts from 12 γ-ray Galactic sources.

Nature 2021 Jun 17;594(7861):33-36. Epub 2021 May 17.

Key Laboratory of Particle Astrophysics & Experimental Physics Division & Computing Center, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.

The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 10 electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. ). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.
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http://dx.doi.org/10.1038/s41586-021-03498-zDOI Listing
June 2021

Convenient hyaluronidase biosensors based on the target-trigger enhancing of the permeability of a membrane using an electronic balance as a readout.

Analyst 2021 May;146(10):3299-3304

Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection for Food Safety, College of Chemistry, Fuzhou University, Fuzhou, Fujian, China.

The change in hyaluronidase (HAase) is related to specific changes in the structure of vitreous, and it is necessary to develop simple but sensitive methods for HAase detection. In this work, a thin film fabricated from a hyaluronic acid (HA)-polyethyleneimine (PEI) hydrogel has been covered on a mixed cellulose microporous membrane (MCEM) to form a HA-PEI-MCEM firstly and it was then applied in a filtration system. The permeability of the filter membrane greatly affects the amount of water passing through within a certain time and the water can be collected and quantitatively measured with a simple electronic balance easily. The low permeability of the HA-PEI-MCEM allows a small amount of water to be drained. But after the addition of HAase, which can hydrolyze HA in the hydrogel, the permeability of the membrane increased. Therefore, the amount of water passing through the HA-PEI-MCEM composite membrane increased accordingly. The composite of the membrane, and the reaction conditions after the addition of HAase were optimized. Under the optimized conditions, the amount of water collected within 5 min showed a linear relationship with the HAase concentration in a range of 1.0-36 U mL-1 with a limit of detection of 0.35 U mL-1.The proposed method has been applied to detect HAase in vitreous samples with satisfactory results.
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http://dx.doi.org/10.1039/d1an00257kDOI Listing
May 2021

Flexible Loop in Carbohydrate-Binding Module 48 Allosterically Modulates Substrate Binding of the 1,4-α-Glucan Branching Enzyme.

J Agric Food Chem 2021 May 14;69(20):5755-5763. Epub 2021 May 14.

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

The 1,4-α-glucan branching enzyme (GBE, EC 2.4.1.18) catalyzes the formation of α-1,6 branching points in starch and plays a key role in synthesis. To obtain mechanistic insights into the catalytic action of the enzyme, we first determined the crystal structure of GBE from STB05 (RoGBE) to a resolution of 2.39 Å (PDB ID: 6JOY). The structure consists of three domains: domain A, domain C, and the carbohydrate-binding module 48 (CBM48). An engineered truncated mutant lacking the CBM48 domain (ΔCBM48) showed significantly reduced ligand binding affinity and enzyme activity. Comparison of the structures of RoGBE with other GBEs showed that CBM48 of RoGBE had a longer flexible loop. Truncation of the flexible loops resulted in reduced binding affinity and activity, thereby substantiating the importance of the optimum loop structure for catalysis. In essence, our study shows that CBM48, especially the flexible loop, plays an important role in substrate binding and enzymatic activity of RoGBE. Further, based on the structural analysis, kinetics, and activity assays on wild type and mutants, as well as homology modeling, we proposed a mechanistic model (called the "lid model") to illustrate how the flexible loop triggers substrate binding, ultimately leading to catalysis.
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http://dx.doi.org/10.1021/acs.jafc.1c00293DOI Listing
May 2021