Publications by authors named "Mengzhu Li"

47 Publications

A rapid method and mechanism to identify the active compounds in Malus micromalus Makino fruit with spectrum-effect relationship, components knock-out and molecular docking technology.

Food Chem Toxicol 2021 Apr 2;150:112086. Epub 2021 Mar 2.

National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng, 475004, Henan, China; Joint International Research Laboratory of Food & Medicine Resource Function, Henan Province, Kaifeng, 475004, China; Functional Food Engineering Technology Research Center, Henan Province, Kaifeng, 475004, China. Electronic address:

Fingerprints of 20 batches of Malus micromalus Makino fruit were established by HPLC coupled with hierarchical cluster analysis (HCA) and principal component analysis (PCA) to estimate the common peaks on the basis of traditional similarity evaluation methods. Chromatographic peaks were identified as p-coumaric acid (P2), ferulic acid glycoside (P6), 4-O-β-Glucopyranosyl-cis-coumaric acid (P8), phloretin-2'-xyloglucoside (P10), phloridzin (P11) and quercetin-3-O-α-rhamnoside (P12) by UPLC-MS/MS method. The results of tyrosinase kinetics experiments showed that: P2 and the concentration of P11 was greater than 0.50 mmol/L mainly had a competitive inhibitory effect on tyrosinase, and the concentration of phlorizin was less than at 0.25 mmol/L, it has a mixed inhibitory effect. P8 was mainly a non-competitive activation type in the concentration range, while P12 was a mixed activation type. The results of tyrosinase molecular docking showed that: P2, P8, P11, P12 was located in the active center of the hydrophobic pocket of the enzyme. They bound to tyrosinase residues by hydrogen bonds and interacted with many hydrophobic residues around them to maintain the structure of the complex. This research provides a rapid method to determine the active compounds in edible plants with the technology of spectrum-effect relationship, component knock-out and molecular docking.
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http://dx.doi.org/10.1016/j.fct.2021.112086DOI Listing
April 2021

Changes and relationship of N-methyladenosine modification and long non-coding RNAs in oxidative damage induced by cadmium in pancreatic β-cells.

Toxicol Lett 2021 Jun 24;343:56-66. Epub 2021 Feb 24.

Institute of Preventive Medicine, School of Public Health, Dali University, Dali, Yunnan, China. Electronic address:

N-methyladenosine (mA) modification and mA-modified Long non-coding RNAs (LncRNAs) play crucial roles in various pathological processes, yet their changes and relationship in cadmium-induced oxidative damage are largely unknown. Here, five mA-modified LncRNAs (LncRNA-TUG1, LncRNA-PVT1, LncRNA-MALAT1, LncRNA-XIST, LncRNA-NEAT1), which have been evidenced to involve in oxidative damage, were selected and their binding proteins were submitted to bioinformatics analysis. Our analysis results showed that these five mA-modified LncRNAs bound to different regulatory proteins of mA modification, implicating that mA modification on LncRNAs may synergistically control by multiple regulatory proteins. Furthermore, the detection data revealed that levels of mA modification, methyltransferase-like 3 (METTL3) and fat mass and obesity-associated protein (FTO) were all significantly decreased in CdSO-induced oxidative damage, which was demonstrated by increasing ROS accumulation and MDA contents as well as decreasing SOD activities. More importantly, LncRNA-MALAT1 and LncRNA-PVT1 indicated downward trend and showed positive relationship with mA modification. Collectively, our results showed that mA modification and mA-modified LncRNAs may involve in oxidative damage induced by cadmium.
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http://dx.doi.org/10.1016/j.toxlet.2021.02.014DOI Listing
June 2021

Phloem loading in rice leaves depends strongly on the apoplastic pathway.

J Exp Bot 2021 Feb 24. Epub 2021 Feb 24.

College of Agriculture, Nanjing Agricultural University, Nanjing, China.

Phloem loading is the first step in sucrose transport from source leaves to sink organs. The phloem loading strategy in rice remains unclear. To determine the potential phloem loading mechanism in rice, yeast invertase (INV) was overexpressed specifically in the cell wall by 35S promoter to block sugar transmembrane loading in rice. The transgenic lines exhibited obvious phloem loading suppression characteristics accompanied by the accumulation of sucrose and starch, restricted vegetative growth and decreased grain yields. The decreased sucrose exudation rate with p-chloromercuribenzenesulfonic acid (PCMBS) treatment also indicated that rice actively transported sucrose into phloem. Moreover, the expression level of OsSUT1 was much higher than that of other plasma membrane localized OsSUTs in the source leaf. Cross sections of the GUS transgenic plant showed that the signals of OsSUT1 and OsSUT5 occurred in the phloem companion cells. The ossut1 and ossut4 mutants presented a decrease of grain yield, implying important roles of OsSUTs in phloem loading. Based on these results, we conclude that rice uses the apoplastic loading as a major phloem loading strategy.
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http://dx.doi.org/10.1093/jxb/erab085DOI Listing
February 2021

The HIV protease inhibitor Saquinavir attenuates sepsis-induced acute lung injury and promotes M2 macrophage polarization via targeting matrix metalloproteinase-9.

Cell Death Dis 2021 Jan 11;12(1):67. Epub 2021 Jan 11.

Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 518116, Shenzhen, China.

Imbalance of macrophage polarization plays an indispensable role in acute lung injury (ALI), which is considered as a promising target. Matrix metalloproteinase-9 (MMP-9) is expressed in the macrophage, and has a pivotal role in secreting inflammatory cytokines. We reported that saquinavir (SQV), a first-generation human immunodeficiency virus-protease inhibitor, restricted exaggerated inflammatory response. However, whether MMP-9 could regulate macrophage polarization and inhibit by SQV is still unknown. We focused on the important role of macrophage polarization in CLP (cecal ligation puncture)-mediated ALI and determined the ability of SQV to maintain M2 over M1 phenotype partially through the inhibition of MMP-9. We also performed a limited clinical study to determine if MMP-9 is a biomarker of sepsis. Lipopolysaccharide (LPS) increased MMP-9 expression and recombinant MMP-9 (rMMP-9) exacerbated LPS-mediated M1 switching. Small interfering RNA to MMP-9 inhibited LPS-mediated M1 phenotype and SQV inhibition of this switching was reversed with rMMP-9, suggesting an important role for MMP-9 in mediating LPS-induced M1 phenotype. MMP-9 messenger RNA levels in peripheral blood mononuclear cells of these 14 patients correlated with their clinical assessment. There was a significant dose-dependent decrease in mortality and ALI after CLP with SQV. SQV significantly inhibited LPS-mediated M1 phenotype and increased M2 phenotype in cultured RAW 264.7 and primary murine bone marrow-derived macrophages as well as lung macrophages from CLP-treated mice. This study supports an important role for MMP-9 in macrophage phenotypic switching and suggests that SQV-mediated inhibition of MMP-9 may be involved in suppressing ALI during systemic sepsis.
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http://dx.doi.org/10.1038/s41419-020-03320-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798387PMC
January 2021

Dexmedetomidine and Clonidine Attenuate Sevoflurane-Induced Tau Phosphorylation and Cognitive Impairment in Young Mice via α-2 Adrenergic Receptor.

Anesth Analg 2021 03;132(3):878-889

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts.

Background: Anesthetic sevoflurane induces tau phosphorylation and cognitive impairment in young mice. The underlying mechanism and the targeted interventions remain largely unexplored. We hypothesized that dexmedetomidine and clonidine attenuated sevoflurane-induced tau phosphorylation and cognitive impairment by acting on α-2 adrenergic receptor.

Methods: Six-day-old mice received anesthesia with 3% sevoflurane 2 hours daily on postnatal days 6, 9, and 12. Alpha-2 adrenergic receptor agonist dexmedetomidine and clonidine were used to treat the mice with and without the α-2 adrenergic receptor antagonist yohimbine. Mouse hippocampi were harvested and subjected to western blot analysis. The New Object Recognition Test and Morris Water Maze were used to measure cognitive function. We analyzed the primary outcomes by using 2- and 1-way analysis of variance (ANOVA) and Mann-Whitney U test to determine the effects of sevoflurane on the amounts of phosphorylated tau, postsynaptic density-95, and cognitive function in young mice after the treatments with dexmedetomidine, clonidine, and yohimbine.

Results: Both dexmedetomidine and clonidine attenuated the sevoflurane-induced increase in phosphorylated tau amount (94 ± 16.3% [dexmedetomidine plus sevoflurane] versus 240 ± 67.8% [vehicle plus sevoflurane], P < .001; 125 ± 13.5% [clonidine plus sevoflurane] versus 355 ± 57.6% [vehicle plus sevoflurane], P < .001; mean ± standard deviation), sevoflurane-induced reduction in postsynaptic density-95 (82 ± 6.6% [dexmedetomidine plus sevoflurane] versus 31 ± 12.4% [vehicle plus sevoflurane], P < .001; 95 ± 6.4% [clonidine plus sevoflurane] versus 62 ± 18.4% [vehicle plus sevoflurane], P < .001), and cognitive impairment in the young mice. Interestingly, yohimbine reversed the effects of dexmedetomidine and clonidine on attenuating the sevoflurane-induced changes in phosphorylated tau, postsynaptic density-95, and cognitive function.

Conclusions: Dexmedetomidine and clonidine could inhibit the sevoflurane-induced tau phosphorylation and cognitive impairment via activation of α-2 adrenergic receptor. More studies are needed to confirm the results and to determine the clinical relevance of these findings.
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http://dx.doi.org/10.1213/ANE.0000000000005268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887006PMC
March 2021

Formation of n → π interaction facilitating dissociative electron transfer in isolated tyrosine-containing molecular peptide radical cations.

Phys Chem Chem Phys 2020 Sep;22(37):21393-21402

Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong SAR, China.

Long-range electron transfer in proteins can be rationalized as a sequential short-distance electron-hopping processes via amino acid residues having low ionization energy as relay stations. Tyrosine residues can serve as such redox-active intermediates through one-electron oxidation to form a π-radical cation at its phenol side chain. An electron transfer from a vicinal functional group to this π-electron hole completes an elementary step of charge migration. However, transient oxidized/reduced intermediates formed at those relay stations during electron transfer processes have not been observed. In this study, formation of analog reactive intermediates via electron donor-acceptor coupling is observed by using IRMPD action spectroscopy. An elementary charge migration at the molecular level in model tyrosine-containing peptide radical cations [M]˙+ in the gas phase is revealed with its unusual Cα-Cβ bond cleavage at the side chain of the N-terminal residue. This reaction is induced by the radical character of the N-terminal amino group (-NH2˙+) resulting from an n → π+ interaction between the nonbonding electron pair of NH2 (n) and the π-electron hole at the Tyr side chain (π+). The formation of -NH2˙+ is supported by the IRMPD spectrum showing a characteristic NH2 scissor vibration coupled with Tyr side-chain stretches at 1577 cm-1. This n → π+ interaction facilitates a dissociative electron transfer with NH2 as the relay station. The occurrence of this side-chain cleavage may be an indicator of the formation of reactive conformers featuring the n → π+ interaction.
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http://dx.doi.org/10.1039/d0cp00533aDOI Listing
September 2020

Tau-induced upregulation of C/EBPβ-TRPC1-SOCE signaling aggravates tauopathies: A vicious cycle in Alzheimer neurodegeneration.

Aging Cell 2020 09 20;19(9):e13209. Epub 2020 Aug 20.

Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Intracellular accumulating of the hyperphosphorylated tau plays a pivotal role in neurodegeneration of Alzheimer disease (AD), but the mechanisms underlying the gradually aggravated tau hyperphosphorylation remain elusive. Here, we show that increasing intracellular tau could upregulate mRNA and protein levels of TRPC1 (transient receptor potential channel 1) with an activated store-operated calcium entry (SOCE), an increased intraneuronal steady-state [Ca ] , an enhanced endoplasmic reticulum (ER) stress, an imbalanced protein kinases and phosphatase, and an aggravated tauopathy. Furthermore, overexpressing TRPC1 induced ER stress, kinases-phosphatase imbalance, tau hyperphosphorylation and cognitive deficits in cultured neurons and mice, while pharmacological inhibiting or knockout TRPC1 attenuated the hTau-induced deregulations in SOCE, ER homeostasis, kinases-phosphatase balance, and tau phosphorylation level with improved synaptic and cognitive functions. Finally, an increased CCAAT-enhancer-binding protein (C/EBPβ) activity was observed in hTau-overexpressing cells and the hippocampus of the AD patients, while downregulating C/EBPβ by siRNA abolished the hTau-induced TRPC1 upregulation. These data reveal that increasing intracellular tau can upregulate C/EBPβ-TRPC1-SOCE signaling and thus disrupt phosphorylating system, which together aggravates tau pathologies leading to a chronic neurodegeneration.
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http://dx.doi.org/10.1111/acel.13209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511862PMC
September 2020

Mechanistic examination of C -C tyrosyl bond cleavage: Spectroscopic investigation of the generation of α-glycyl radical cations from tyrosyl (glycyl/alanyl)tryptophan.

J Mass Spectrom 2020 Jul 28;56(4):e4630. Epub 2020 Jul 28.

Department of Chemistry, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

In this study, dissociative one-electron transfer dissociation of [Cu (dien)Y(G/A)W] [dien = diethylenetriamine; Y(G/A)W = tyrosyl (glycyl/alanyl)tryptophan] was used to generate the tripeptide radical cations [Y(G/A)W] ; subsequent loss of the Tyr side chain formed [G (G/A)W] . The π-centered species [YGW ] generated the α-centered species [G GW] through C -C bond cleavage, as revealed using infrared multiple photon dissociation (IRMPD) measurements and density functional theory (DFT) calculations. Comparisons of experimental and theoretical IR spectra confirmed that both the charge and spin densities of [Y(G/A)W ] were delocalized initially at the tryptophan indolyl ring; subsequent formation of the final [G (G/A)W] structure gave the highest spin density at the α-carbon atom of the N-terminal glycine residue, with a proton solvated by the first amide oxygen atom. The IRMPD mass spectra and action spectra of the [G (G/A)W] species were all distinctly different from those of their isomeric [G(G/A)W ] species. The mechanism of formation of the captodative [G (G/A)W] species-with the charge site separated from the radical site-from [Y(G/A)W ] has been elucidated. DFT calculations suggested that the C -C bond cleavage of the tyrosine residue in the radical cationic [Y(G/A)W ] precursor involves (a) through-space electron transfer between the indolyl and phenolic groups; (b) formation of proton-bound dimers through C -C cleavage of the tyrosine residue; and (c) a concerted proton rearrangement from the phenolic OH group to the carboxyl group and formation of the α-carbon-centered product [G (G/A)W] through hydrogen bond cleavage. The barriers for the electron transfer (a), the C -C cleavage (b), and the protonation rearrangement (c) were 12.8, 26.5, and 10.3 kcal mol , respectively.
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http://dx.doi.org/10.1002/jms.4630DOI Listing
July 2020

Tau Contributes to Sevoflurane-induced Neurocognitive Impairment in Neonatal Mice.

Anesthesiology 2020 09;133(3):595-610

From the Department of Anesthesia, Tianjin Medical University General Hospital, Tianjin, China (Yang Yu, Y. Yang, Yonghao Yu) the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts (Yang Yu, Y. Yang, H.T., F.H., L.L., M.L., Y.D., Y.Z., Z.X.) the Department of Anesthesia, Xinhua Hospital of Shanghai Jiaotong University, Shanghai, China (H.T.) the Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (M.B., W.H.) the Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (A.K.) the Department of Anesthesia, Second Affiliated Hospital of Nanchang University, Nanchang, China (F.H.) Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China (L.L.) Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China (M.L.) the Department of Anesthesiology, Columbia University Medical Center, New York, New York (G.Y.).

Background: Sevoflurane anesthesia induces Tau phosphorylation and cognitive impairment in neonatal but not in adult mice. This study tested the hypothesis that differences in brain Tau amounts and in the activity of mitochondria-adenosine triphosphate (ATP)-Nuak1-Tau cascade between the neonatal and adult mice contribute to the age-dependent effects of sevoflurane on cognitive function.

Methods: 6- and 60-day-old mice of both sexes received anesthesia with 3% sevoflurane for 2 h daily for 3 days. Biochemical methods were used to measure amounts of Tau, phosphorylated Tau, Nuak1, ATP concentrations, and mitochondrial metabolism in the cerebral cortex and hippocampus. The Morris water maze test was used to evaluate cognitive function in the neonatal and adult mice.

Results: Under baseline conditions and compared with 60-day-old mice, 6-day-old mice had higher amounts of Tau (2.6 ± 0.4 [arbitrary units, mean ± SD] vs. 1.3 ± 0.2; P < 0.001), Tau oligomer (0.3 ± 0.1 vs. 0.1 ± 0.1; P = 0.008), and Nuak1 (0.9 ± 0.3 vs. 0.3 ± 0.1; P = 0.025) but lesser amounts of ATP (0.8 ± 0.1 vs. 1.5 ± 0.1; P < 0.001) and mitochondrial metabolism (74.8 ± 14.1 [pmol/min] vs. 169.6 ± 15.3; P < 0.001) in the cerebral cortex. Compared with baseline conditions, sevoflurane anesthesia induced Tau phosphorylation at its serine 202/threonine 205 residues (1.1 ± 0.4 vs. 0.2 ± 0.1; P < 0.001) in the 6-day-old mice but not in the 60-day-old mice (0.05 ± 0.04 vs. 0.03 ± 0.01; P = 0.186). The sevoflurane-induced Tau phosphorylation and cognitive impairment in the neonatal mice were both attenuated by the inhibition of Nuak1 and the treatment of vitamin K2.

Conclusions: Higher brain Tau concentrations and lower brain mitochondrial metabolism in neonatal compared with adult mice contribute to developmental stage-dependent cognitive dysfunction after sevoflurane anesthesia.
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http://dx.doi.org/10.1097/ALN.0000000000003452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429299PMC
September 2020

Sevoflurane induces neuronal activation and behavioral hyperactivity in young mice.

Sci Rep 2020 07 8;10(1):11226. Epub 2020 Jul 8.

Department of Anesthesia, Critical Care and Pain Medicine; Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129-2060, USA.

Sevoflurane, a commonly used anesthetic, may cause agitation in patients. However, the mechanism underlying this clinical observation remains largely unknown. We thus assessed the effects of sevoflurane on neuronal activation and behaviors in mice. Ten-day-old mice received 2% sevoflurane, 1% isoflurane, or 6% desflurane for 10 minutes. The behavioral activities were recorded and evaluated at one minute after the loss of righting reflex in the mice, which was about two minutes after the anesthetic administration. The neuronal activation was evaluated by c-Fos expression and calcium imaging at one minute after the anesthetic administration. Propofol, which reduces neuronal activation, was used to determine the cause-and-effect of sevoflurane. We found that sevoflurane caused an increase in neuronal activation in primary somatosensory cortex of young mice and behavioral hyperactivity in the mice at one minute after the loss of righting reflex. Desflurane did not induce behavioral hyperactivity and isoflurane only caused behavioral hyperactivity with borderline significance. Finally, propofol attenuated the sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These results demonstrate an unexpected sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These findings suggest the potential mechanisms underlying the sevoflurane-induced agitation and will promote future studies to further determine whether anesthetics can induce behavioral hyperactivity via increasing neuronal activation.
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http://dx.doi.org/10.1038/s41598-020-66959-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343864PMC
July 2020

Implementation of a multiple-fraction concatenation strategy in an online two-dimensional high-/low-pH reversed-phase/reversed-phase liquid chromatography platform for qualitative and quantitative shotgun proteomic analyses.

J Mass Spectrom 2020 Jun 12;56(4):e4591. Epub 2020 Jun 12.

Department of Chemistry, The University of Hong Kong, Hong Kong, China.

Multidimensional liquid chromatography is the mainstay separation technique used for shotgun proteomic analyses. The application of a multiple-fraction concatenation (MFC) strategy can result in a more disperse and consistent peptide elution profile across different fractions, when compared with a conventional strategy. Herein, we present the first automated online RP-RP platform implementing an MFC strategy to facilitate robust, unattended, routine proteomic analyses. The improved duty cycle utilization of the MFC strategy led to an increase of 9% in the separation space occupancy and increases of approximately 10% in the identification of both proteins and peptides. The peptides uniquely identified by the MFC strategy were significantly biased toward those of acidic nature, with increased precursor signals leading to improved MS/MS spectral quality and enhanced acidic peptide identification. These improvements in qualitative analysis using the MFC strategy were also extended to quantitative analysis. When the acquired proteome was quantified with a normalized spectral abundance factor, the additionally acquired acidic peptides were a critical factor leading to enhanced reproducibility of quantitation using the MFC strategy. With merits of superior qualitative and quantitative characteristics over the conventional strategy, the MFC strategy appears to be a highly amenable technique for enhancing the separation capacity for routine proteomic analyses.
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http://dx.doi.org/10.1002/jms.4591DOI Listing
June 2020

rPTMDetermine: A Fully Automated Methodology for Endogenous Tyrosine Nitration Validation, Site-Localization, and Beyond.

Anal Chem 2020 08 21;92(15):10768-10776. Epub 2020 Jul 21.

Department of Chemistry, The University of Hong Kong, Pokfulam, Hong Kong, China.

We present herein rPTMDetermine, an adaptive and fully automated methodology for validation of the identification of rarely occurring post-translational modifications (PTMs), using a semisupervised approach with a linear discriminant analysis (LDA) algorithm. With this strategy, verification is enhanced through similarity scoring of tandem mass spectrometry (MS/MS) comparisons between modified peptides and their unmodified analogues. We applied rPTMDetermine to (1) perform fully automated validation steps for modified peptides identified from an database and (2) retrieve potential yet-to-be-identified modified peptides from raw data (that had been missed through conventional database searches). In part (1), 99 of 125 3-nitrotyrosyl-containing (nitrated) peptides obtained from a ProteinPilot search were validated and localized. Twenty nitrated peptides were falsely assigned because of incorrect monoisotopic peak assignments, leading to erroneous identification of deamidation and nitration. Five additional nitrated peptides were, however, validated after performing nonmonoisotopic peak correction. In part (2), an additional 236 unique nitrated peptides were retrieved and localized, containing 113 previously unreported nitration sites; 25 endogenous nitrated peptides with novel sites were selected and verified by comparison with synthetic analogues. In summary, we identified and confidently validated 296 unique nitrated peptides-collectively representing the largest number of endogenously identified 3-nitrotyrosyl-containing peptides from the cerebral cortex proteome of a model of stroke. Furthermore, we harnessed the rPTMDetermine strategy to complement conventional database searching and enhance the confidence of assigning rarely occurring PTMs, while recovering many missed peptides. In a final demonstration, we successfully extended the application of rPTMDetermine to peptides featuring tryptophan oxidation.
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http://dx.doi.org/10.1021/acs.analchem.0c02148DOI Listing
August 2020

Dissociative electron transfer of copper(ii) complexes of glycyl(glycyl/alanyl)tryptophan in vacuo: IRMPD action spectroscopy provides evidence of transition from zwitterionic to non-zwitterionic peptide structures.

Phys Chem Chem Phys 2020 Jun 3;22(23):13084-13091. Epub 2020 Jun 3.

Department of Chemistry, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

We report herein the first detailed study of the mechanism of redox reactions occurring during the gas-phase dissociative electron transfer of prototypical ternary [Cu(dien)M]˙ complexes (M, peptide). The two final products are (i) the oxidized non-zwitterionic π-centered [M]˙ species with both the charge and spin densities delocalized over the indole ring of the tryptophan residue and with a C-terminal COOH group intact, and (ii) the complementary ion [Cu(dien)]. Infrared multiple photon dissociation (IRMPD) action spectroscopy and low-energy collision-induced dissociation (CID) experiments, in conjunction with density functional theory (DFT) calculations, revealed the structural details of the mass-isolated precursor and product cations. Our experimental and theoretical results indicate that the doubly positively charged precursor [Cu(dien)M]˙ features electrostatic coordination through the anionic carboxylate end of the zwitterionic M moiety. An additional interaction exists between the indole ring of the tryptophan residue and one of the primary amino groups of the dien ligand; the DFT calculations provided the structures of the precursor ion, intermediates, and products, and enabled us to keep track of the locations of the charge and unpaired electron. The dissociative one-electron transfer reaction is initiated by a gradual transition of the M tripeptide from the zwitterionic form in [Cu(dien)M]˙ to the non-zwitterionic M intermediate, through a cascade of conformational changes and proton transfers. In the next step, the highest energy intermediate is formed; here, the copper center is 5-coordinate with coordination from both the carboxylic acid group and the indole ring. A subsequent switch back to 4-coordination to an intermediate IM1, where attachment to GGW occurs through the indole ring only, creates the structure that ultimately undergoes dissociation.
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http://dx.doi.org/10.1039/d0cp02296aDOI Listing
June 2020

A Photoactivated Cu-CeO Catalyst with Cu-[O]-Ce Active Species Designed through MOF Crystal Engineering.

Angew Chem Int Ed Engl 2020 May 25;59(21):8203-8209. Epub 2020 Feb 25.

Beijing National Laboratory for Molecular Sciences, State Key laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.

Fully utilizing solar energy for catalysis requires the integration of conversion mechanisms and therefore delicate design of catalyst structures and active species. Herein, a MOF crystal engineering method was developed to controllably synthesize a copper-ceria catalyst with well-dispersed photoactive Cu-[O]-Ce species. Using the preferential oxidation of CO as a model reaction, the catalyst showed remarkably efficient and stable photoactivated catalysis, which found practical application in feed gas treatment for fuel cell gas supply. The coexistence of photochemistry and thermochemistry effects contributes to the high efficiency. Our results demonstrate a catalyst design approach with atomic or molecular precision and a combinatorial photoactivation strategy for solar energy conversion.
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http://dx.doi.org/10.1002/anie.201916049DOI Listing
May 2020

Tau acetylates and stabilizes β-catenin thereby promoting cell survival.

EMBO Rep 2020 03 13;21(3):e48328. Epub 2020 Jan 13.

Key Laboratory of Ministry of Education of China for Neurological Disorders, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Overexpressing Tau counteracts apoptosis and increases dephosphorylated β-catenin levels, but the underlying mechanisms are elusive. Here, we show that Tau can directly and robustly acetylate β-catenin at K49 in a concentration-, time-, and pH-dependent manner. β-catenin K49 acetylation inhibits its phosphorylation and its ubiquitination-associated proteolysis, thus increasing β-catenin protein levels. K49 acetylation further promotes nuclear translocation and the transcriptional activity of β-catenin, and increases the expression of survival-promoting genes (bcl2 and survivin), counteracting apoptosis. Mutation of Tau's acetyltransferase domain or co-expressing non-acetylatable β-catenin-K49R prevents increased β-catenin signaling and abolishes the anti-apoptotic function of Tau. Our data reveal that Tau preserves β-catenin by acetylating K49, and upregulated β-catenin/survival signaling in turn mediates the anti-apoptotic effect of Tau.
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http://dx.doi.org/10.15252/embr.201948328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054687PMC
March 2020

RNAi-Mediated Gene Silencing of Induces a Hyperbranching Phenotype in .

J Microbiol Biotechnol 2020 Feb;30(2):206-215

Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, P.R. China.

is the major filamentous fungus used to produce cellulase and there is huge interest in promoting its ability to produce higher titers of cellulase. Among the many factors affecting cellulase production in , the mycelial phenotype is important but seldom studied. Herein, a close homolog of the COT1 kinase was discovered in and designated COT1, which is of 83.3% amino acid sequence identity. Functional disruption of in by RNAi-mediated gene silencing resulted in retarded sporulation on potato dextrose agar and dwarfed colonies on minimal medium agar plates containing glucose, xylan, lactose, xylose, or glycerol as the sole carbon source. The representative mutant strain, SUS2/Trcot1i, also displayed reduced mycelia accumulation but hyperbranching in the MM glucose liquid medium, with hyphal growth unit length values decreased to 73.0 µm/tip compared to 239.8 µm/tip for the parent strain SUS2. The hyperbranching phenotype led to slightly but significantly increased cellulase secretion from 24 to 72 h in a batch culture. However, the cellulase production per unit of mycelial biomass was much more profoundly improved from 24 to 96 h.
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http://dx.doi.org/10.4014/jmb.1909.09050DOI Listing
February 2020

Single-shot coherent power-spectrum imaging of objects hidden by opaque scattering media.

Appl Opt 2019 Feb;58(4):1033-1039

We report coherent imaging of objects behind opaque scattering media with only one piece of the power spectrum pattern. We solve the unique solution and improve algorithm speed for the inverse problem. Based on the proposed scattering-disturbance model, with only one piece of the Fourier transform power spectrum pattern under coherent illumination, we successfully reconstruct clear images of the objects fully hidden by an opaque diffuser. The experimental results demonstrate the feasibility of the reconstruction method and the scattering-disturbance model. Our method makes it possible to carry out snapshot coherent imaging of the objects obscured by scattering media, which extends the methodology of x-ray crystallography to visible-light scattering imaging for underwater and living biomedical imaging.
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http://dx.doi.org/10.1364/AO.58.001033DOI Listing
February 2019

Enriched gestation activates the IGF pathway to evoke embryo-adult benefits to prevent Alzheimer's disease.

Transl Neurodegener 2019 5;8. Epub 2019 Mar 5.

1Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China.

Background: Building brain reserves before dementia onset could represent a promising strategy to prevent Alzheimer's disease (AD), while how to initiate early cognitive stimulation is unclear. Given that the immature brain is more sensitive to environmental stimuli and that brain dynamics decrease with ageing, we reasoned that it would be effective to initiate cognitive stimulation against AD as early as the fetal period.

Methods: After conception, maternal AD transgenic mice (3 × Tg AD) were exposed to gestational environment enrichment (GEE) until the day of delivery. The cognitive capacity of the offspring was assessed by the Morris water maze and contextual fear-conditioning tests when the offspring were raised in a standard environment to 7 months of age. Western blotting, immunohistochemistry, real-time PCR, immunoprecipitation, chromatin immunoprecipitation (ChIP) assay, electrophysiology, Golgi staining, activity assays and sandwich ELISA were employed to gain insight into the mechanisms underlying the beneficial effects of GEE on embryos and 7-10-month-old adult offspring.

Results: We found that GEE markedly preserved synaptic plasticity and memory capacity with amelioration of hallmark pathologies in 7-10-m-old AD offspring. The beneficial effects of GEE were accompanied by global histone hyperacetylation, including those at promoter-binding regions, with robust BDNF mRNA and protein expression in both embryo and progeny hippocampus. GEE increased insulin-like growth factor 1 (IGF1) and activated its receptor (IGF1R), which phosphorylates Ca/calmodulin-dependent kinase IV (CaMKIV) at tyrosine sites and triggers its nuclear translocation, subsequently upregulating histone acetyltransferase (HAT) and BDNF transcription. The upregulation of IGF1 mimicked the effects of GEE, while IGF1R or HAT inhibition during pregnancy abolished the GEE-induced CaMKIV-dependent histone hyperacetylation and BDNF upregulation.

Conclusions: These findings suggest that activation of IGF1R/CaMKIV/HAT/BDNF signaling by gestational environment enrichment may serve as a promising strategy to delay AD progression.
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http://dx.doi.org/10.1186/s40035-019-0149-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399936PMC
March 2019

ER stress contributes to high-fat diet-induced decrease of thyroglobulin and hypothyroidism.

Am J Physiol Endocrinol Metab 2019 03 8;316(3):E510-E518. Epub 2019 Jan 8.

Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Ji-nan, Shandong , China.

Recent studies revealed the emerging role of excess uptake of lipids in the development of hypothyroidism. However, the underlying mechanism is largely unknown. We investigated the effect of high-fat diet (HFD) on thyroid function and the role of endoplasmic reticulum (ER) in HFD-induced hypothyroidism. Male Sprague-Dawley rats were fed with HFD or control diet for 18 wk. HFD rats showed an impaired thyroid function, with decreased thyroglobulin (Tg) level. We found the ER stress was triggered in HFD rat thyroid glands and palmitate-treated thyrocytes. Luminal swelling of ER in thyroid epithelial cells of HFD rats was also observed. The rate of Tg degradation increased in palmitate-treated thyrocytes. In addition, applying 4-phenyl butyric acid to alleviate ER stress in HFD rats improved the decrease of Tg and thyroid function. Withdrawal of the HFD improved thyroid function . In conclusion, we demonstrate that ER stress mediates the HFD-induced hypothyroidism, probably by impairing the production of Tg, and attenuation of ER stress improves thyroid function. Our study provides the understanding of how HFD induces hypothyroidism.
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http://dx.doi.org/10.1152/ajpendo.00194.2018DOI Listing
March 2019

Development of Betaine-Based Sustainable Catalysts for Green Conversion of Carbohydrates and Biomass into 5-Hydroxymethylfurfural.

ChemSusChem 2019 Jan 2;12(2):495-502. Epub 2019 Jan 2.

College of Energy, Xiamen University, Xiamen, 361102, P.R.China.

Renewable and sustainable betaine-based catalysts (BX) derived from the betaine sugar industry or ChCl were developed for the production of 5-hydroxymethylfurfural (HMF) from various carbohydrates. The HMF yields in the BX-based media reached up to 88 %, 66 %, 37 % and 53 %, for the conversion of fructose, glucose, cellulose, and lignocellulosic biomass, respectively. In addition, choline-O-sulfate was synthesized and demonstrated to be an efficient catalyst for the conversion of fructose to HMF. From the perspective of green and sustainable chemistry, this work demonstrates benefits not only in the preparation of sustainable catalysts but also the green production of HMF from biomass.
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http://dx.doi.org/10.1002/cssc.201802342DOI Listing
January 2019

Ultrasound-Assisted Technology Versus the Conventional Landmark Location Method in Spinal Anesthesia for Cesarean Delivery in Obese Parturients: A Randomized Controlled Trial.

Anesth Analg 2019 07;129(1):155-161

From the Department of Anesthesiology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.

Background: Spinal anesthesia, which is commonly used in cesarean deliveries, is often difficult to perform in obese parturients because of poorly palpable surface landmarks and positioning challenges. This study aimed to evaluate the benefits of ultrasound-assisted technology for performing spinal anesthesia in obese parturients.

Methods: Parturients with a body mass index (BMI) ≥30 kg/m scheduled for elective cesarean delivery were randomized to undergo spinal anesthesia using the conventional landmark location technique (landmark group, n = 40) or prepuncture ultrasound examination (ultrasound group, n = 40). All participants underwent spinal anesthesia in the lateral position. The primary outcome was the first-attempt success rate. Secondary outcomes were the number of skin punctures and needle passes, procedure times, patient satisfaction, changes in the intended interspace, and incidence of complications.

Results: The ultrasound group had a significantly higher first-attempt success rate (87.5% vs 52.5%; P = .001), fewer cases requiring >10 needle passes (1 vs 17; P < .001), and fewer skin punctures and needle passes (P < .001 for both). There was no statistically significant difference in the time taken to identify the needle insertion site between the 2 groups (202.5 vs 272.0 seconds; P = .580). Both the spinal injection time and total procedure time were significantly longer in the landmark group (P < .001). Patient satisfaction scores were significantly higher in the ultrasound group (P = .001). Among patients with BMI between 30 and 34.9 kg/m, there was no statistically significant difference in the first-attempt success rate (P = .407), number of cases with >10 needle passes (P = .231), spinal injection time (P = .081), or total procedure time (P = .729); however, more time was required to identify the needle insertion site in the ultrasound group (P < .001). For patients with BMI between 35 and 43 kg/m, the ultrasound group had a significantly higher first-attempt success rate (P ≤ .041), fewer cases with >10 needle passes (P ≤ .01), and shorter procedure times, including the time required to identify the needle insertion site (P < .001).

Conclusions: Prepuncture ultrasound examination can facilitate spinal anesthesia in the lateral position in obese parturients (35 kg/m ≤ BMI ≤ 43 kg/m) by improving the first-attempt success rate, reducing the number of needle passes and puncture attempts, shortening the total procedure time, and improving patient satisfaction.
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http://dx.doi.org/10.1213/ANE.0000000000003795DOI Listing
July 2019

Reductive Transformation of Layered-Double-Hydroxide Nanosheets to Fe-Based Heterostructures for Efficient Visible-Light Photocatalytic Hydrogenation of CO.

Adv Mater 2018 Jul 31:e1803127. Epub 2018 Jul 31.

Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.

Conversion of syngas (CO, H ) to hydrocarbons, commonly known as the Fischer-Tropsch (FT) synthesis, represents a fundamental pillar in today's chemical industry and is typically carried out under technically demanding conditions (1-3 MPa, 300-400 °C). Photocatalysis using sunlight offers an alternative and potentially more sustainable approach for the transformation of small molecules (H O, CO, CO , N , etc.) to high-valuable products, including hydrocarbons. Herein, a novel series of Fe-based heterostructured photocatalysts (Fe-x) is successfully fabricated via H reduction of ZnFeAl-layered double hydroxide (LDH) nanosheets at temperatures (x) in the range 300-650 °C. At a reduction temperature of 500 °C, the heterostructured photocatalyst formed (Fe-500) consists of Fe and FeO nanoparticles supported by ZnO and amorphous Al O . Fe-500 demonstrates remarkable CO hydrogenation performance with very high initial selectivities toward hydrocarbons (89%) and especially light olefins (42%), and a very low selectivity towards CO (11%). The intimate and abundant interfacial contacts between metallic Fe and FeO in the Fe-500 photocatalyst underpins its outstanding photocatalytic performance. The photocatalytic production of high-value light olefins with suppressed CO selectivity from CO hydrogenation is demonstrated here.
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http://dx.doi.org/10.1002/adma.201803127DOI Listing
July 2018

End-tidal carbon dioxide monitoring improves patient safety during propofol-based sedation for breast lumpectomy: A randomised controlled trial.

Eur J Anaesthesiol 2018 11;35(11):848-855

Background: The use of sedation is becoming more commonplace. Although pulse oximetry is a standard monitoring procedure during sedation, it cannot accurately detect early hypoventilation. End-tidal carbon dioxide (EtCO2) monitoring can be an earlier indicator of airway compromise; however, the existing literature is limited to a few studies with varying outcomes.

Objectives: To evaluate whether EtCO2 monitoring decreases the incidences of CO2 retention and apnoeic events in propofol-based sedation.

Design: Randomised controlled study.

Setting: A tertiary hospital.

Patients: Two hundred women (aged 18 to 65 years, ASA physical status 1 or 2) who were scheduled for breast lumpectomy between June 2017 and August 2017.

Interventions: Patients were allocated randomly to receive either standard monitoring or standard monitoring and EtCO2 monitoring.

Main Outcome Measures: The primary outcome was the incidence of CO2 retention. The secondary outcomes were the number of actions taken to restore ventilation, variations in PaCO2 and pH, the frequency of apnoea and the recovery time.

Results: CO2 retention occurred significantly less often in the EtCO2 monitoring group (10 vs. 87%; P < 0.0001). In the standard monitoring group, the mean PaCO2 was more than 6 kPa (45 mmHg) and the pH was less than 7.35 at 5, 10, 20 and 30 min after induction of anaesthesia and at the end of the procedure. Both values were within the normal range in the EtCO2 monitoring group. The number of airway interventions performed was significantly higher in the EtCO2 monitoring group (9.8 ± 1.8 vs. 1.9 ± 1.0; P < 0.0001). Apnoea occurred significantly less often in the EtCO2 monitoring group (0 vs. 10%; P < 0.0001) and recovery time was shorter (9.9 ± 1.4 vs. 11.4 ± 2.1 min; P = 0.048).

Conclusion: The addition of EtCO2 monitoring to standard monitoring during propofol-based sedation can improve patient safety by decreasing the incidence of CO2 retention, and therefore the risk of hypoxaemia through early recognition of apnoea, and can also shorten recovery time.

Trial Registration: This trial is registered with http://www.chictr.org.cn (ChiCTR-INR-17011537).
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http://dx.doi.org/10.1097/EJA.0000000000000859DOI Listing
November 2018

Up-conversion luminescence, thermometry, and optical heating properties of Er- and Yb-doped KLaNbO submicro-particles synthesized by a simple molten salt method.

Dalton Trans 2018 Aug;47(33):11337-11345

College of Science, Civil Aviation University of China, Tianjin 300300, China.

A series of Er3+- and Yb3+-doped K2LaNb5O15 (KLN:xEr3+/Yb3+) up-conversion (UC) submicro-particles have been synthesized for the first time by a simple and low-cost molten salt (MS) approach. X-ray diffraction (XRD) was performed to analyze the phase and structure, and the prepared KLN:xEr3+/Yb3+ samples exhibited a single phase tetragonal tungsten bronze (TTB) structure. The morphologies were characterized by scanning electron microscopy (SEM), and submicro-rod-like particles were obtained for all samples. Under 980 nm excitation, KLN:xEr3+/Yb3+ emitted bright green and weak red emissions which arose from the intra-4f transitions of Er3+ ions. The UC emission intensities and RR/G (the intensity ratio between red and green emissions) were disclosed to be tightly dependent on the Yb3+ ion concentration, and the involved UC luminescence mechanism was studied. Meanwhile, the slope of log I-log P plots displayed an evident reduction with a Ts (sintering temperature) increase, which was ascribed to the saturation effect coming from the competition between UC processes and linear decay. Furthermore, temperature-dependent UC behavior and temperature sensing properties of KLN:xEr3+/Yb3+ were probed based on the fluorescence intensity ratio (FIR) technique of UC green emission. The maximum sensor sensitivity (S) of KLN:0.04Er3+/Yb3+ (Ts = 900 °C) and KLN:0.16Er3+/Yb3+ (Ts = 900 °C) was determined to be as high as 10.90 × 10-3 and 12.27 × 10-3 K-1, respectively. We also showed that the particle size has an evident influence on S, which can be qualitatively interpreted by J-O theory. Thermal-cycling measurements were conducted at different temperatures, and good reliability and repeatability were confirmed. In addition, an obvious optical heating effect was also realized and the variation of temperature induced with a laser was about 32 K. These results reveal that KLN:xEr3+/Yb3+ submicroparticles with high sensor sensitivity and an obvious laser-induced thermal effect are suitable for future optical thermometers and optical heaters.
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http://dx.doi.org/10.1039/c8dt02069hDOI Listing
August 2018

TRPC1 Null Exacerbates Memory Deficit and Apoptosis Induced by Amyloid-β.

J Alzheimers Dis 2018 ;63(2):761-772

Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Key Laboratory of Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The transient receptor potential cation (TRPC) channels are widely expressed in nervous system but their functions remain largely unclear. Here, we found that TRPC1 deletion did not affect learning and memory in physiological conditions, while it aggravated learning and memory deficits induced by amyloid-β (Aβ), the major component of the senile plaques observed in the brains of Alzheimer's disease (AD). Further studies demonstrated that TRPC1 deletion did not affect cell apoptosis in physiological condition, but it exacerbated the Aβ-induced cell death in mouse hippocampus. Moreover, the level of TRPC1 was decreased in AD cell and mouse models, and upregulation of TRPC1 decreased Aβ levels with attenuation of apoptosis in the cells stably overexpressing amyloid-β protein precursor (AβPP). Finally, the transmembrane domain of TRPC1 could bind to AβPP and thus decreased Aβ production. These findings indicate that loss of TRPC1 exacerbates Aβ-induced memory deficit and cell apoptosis, though it does not impair cognitive function or induce cell death in physiological conditions.
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http://dx.doi.org/10.3233/JAD-180077DOI Listing
June 2019

Biochemical and mutational analyses of a Trametes pyranose oxidase and comparison of its mutants in breadmaking.

AMB Express 2018 Mar 13;8(1):38. Epub 2018 Mar 13.

Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, No. 12 South Zhongguancun Street, Beijing, 100081, People's Republic of China.

Pyranose oxidase (POx) is a homotetrameric flavoprotein that catalyzes the oxidation of pyranose-configured sugars at position C-2 to corresponding 2-ketoaldoses. The wide substrate specificity makes POx potential for application in various biotechnological industries. In the present study we reported the gene cloning and heterologous expression of a POx from the basidiomycete Trametes sp. and functionally expressed the gene in Escherichia coli BL21(DE3). Based on sequence alignment, three residues were chosen for site-directed mutagenesis to obtain two single mutants (K312E and E539K) and two double mutants (T166A/E539K and K312E/E539K). In comparison to the wild-type, K312E shifted its optimal pH to 5.5 while the optimal temperature of E539K and K312E/E539K increased by 10 °C. The mutants retained more activities over broader pH ranges and higher temperatures and catalyzed D-glucose at higher efficiency (5800‒12,667 M s for the mutants versus 5083 M s for the wild-type). The recombinant POx and its mutants were all useful in gluten agglomeration and enlarging the loaf volume, which depends on the amounts of enzymes added. Interestingly, adding the same amount (0.5 nkat/g of flour) of wild-type and mutant enzymes differed in the change of loaf volumes, pinpointing that the catalytic activity is not the sole determinant in applying POx in breadmaking.
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http://dx.doi.org/10.1186/s13568-018-0570-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849585PMC
March 2018

Hybrid Au-Ag Nanostructures for Enhanced Plasmon-Driven Catalytic Selective Hydrogenation through Visible Light Irradiation and Surface-Enhanced Raman Scattering.

J Am Chem Soc 2018 01 11;140(3):864-867. Epub 2018 Jan 11.

Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University , Beijing 100871, China.

Herein, we report the successful application of hybrid Au-Ag nanoparticles (NPs) and nanochains (NCs) in the harvesting of visible light energy for selective hydrogenation reactions. For individual Au@Ag NPs with Au25 cores, the conversion and turnover frequency (TOF) are approximately 8 and 10 times higher than those of Au25 NPs, respectively. Notably, after the self-assembly of the Au@Ag NPs, the conversion and TOF of 1D NCs were approximately 2.5 and 2 times higher than those of isolated Au@Ag NPs, respectively, owing to the coupling of surface plasmon and the increase in the rate at which hot (energetic) electrons are generated with the formation of plasmonic hot spots between NPs. Furthermore, the surface-enhanced Raman scattering (SERS) activity of 1D Au@Ag NCs was strengthened by nearly 2 orders of magnitude.
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http://dx.doi.org/10.1021/jacs.7b11293DOI Listing
January 2018

Efficient Coproduction of Mannanase and Cellulase by the Transformation of a Codon-Optimized Endomannanase Gene from Aspergillus niger into Trichoderma reesei.

J Agric Food Chem 2017 Dec 8;65(50):11046-11053. Epub 2017 Dec 8.

Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences , Beijing 100081, China.

Cellulase and mannanase are both important enzyme additives in animal feeds. Expressing the two enzymes simultaneously within one microbial host could potentially lead to cost reductions in the feeding of animals. For this purpose, we codon-optimized the Aspergillus niger Man5A gene to the codon-usage bias of Trichoderma reesei. By comparing the free energies and the local structures of the nucleotide sequences, one optimized sequence was finally selected and transformed into the T. reesei pyridine-auxotrophic strain TU-6. The codon-optimized gene was expressed to a higher level than the original one. Further expressing the codon-optimized gene in a mutated T. reesei strain through fed-batch cultivation resulted in coproduction of cellulase and mannanase up to 1376 U·mL and 1204 U·mL, respectively.
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http://dx.doi.org/10.1021/acs.jafc.7b05114DOI Listing
December 2017

Ginkgo biloba Extract EGb761 Attenuates Hyperhomocysteinemia-induced AD Like Tau Hyperphosphorylation and Cognitive Impairment in Rats.

Curr Alzheimer Res 2018 ;15(1):89-99

Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030. China.

Background: Ginkgo biloba extract EGb761 has shown the neuroprotective effects on Alzheimer's disease (AD) through the protection against the Aβ-induced neurotoxicity. However, it is not completedly clear whether EGb761 attenuates tau hyperphosphorylation, another of the most prominent mechanisms underlying the pathology of AD.

Methods: we employed hyperhomocysteinemia (HHcy) to mimic AD like pathological alterations and memory deficits in rats as model, and injected EGb761 with or after HHcy injection as prevention and treatment, injected saline as control. We measured the status of oxidative damage and spatial and learning memory in rats. Then we detected the level of memory-related proteins, tau phosphorylation and the level and activity of tau kinase (GSK-3β) and phosphatase (PP2A) by Western blotting and Immunohistochemistry.

Results: We found that EGb761 could significantly antagonize HHcy-induced oxidative damage, recover PP2Ac and GSK3β activities deregulated by HHcy. Furthermore, tau was hyperphosphorylated at Thr231, Ser262, Ser396, and Ser404, most common PP2Ac and GSK3β targeted sites in the hippocampus and prefrontal cortex of HHcy rats, whereas EGb761 recovered the tau phosphorylation at those sites. Behavioral tests revealed that EGb761 rescued HHcy-induced spatial reference memory deficit and upregulated the expression of synapse-associated protein PSD95 and synapsin-1.

Conclusion: EGb761 might be a promising drug to treat AD through its anti-oxidative activity and decreasing tau hyperphosphorylation besides the protection against the Aβ-induced neurotoxicity.
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http://dx.doi.org/10.2174/1567205014666170829102135DOI Listing
March 2019

GSK-3β deletion in dentate gyrus excitatory neuron impairs synaptic plasticity and memory.

Sci Rep 2017 07 18;7(1):5781. Epub 2017 Jul 18.

Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China.

Increasing evidence suggests that glycogen synthase kinase-3β (GSK-3β) plays a crucial role in neurodegenerative/psychiatric disorders, while pan-neural knockout of GSK-3β also shows detrimental effects. Currently, the function of GSK-3β in specific type of neurons is elusive. Here, we infused AAV-CaMKII-Cre-2A-eGFP into GSK-3β mice to selectively delete the kinase in excitatory neurons of hippocampal dentate gyrus (DG), and studied the effects on cognitive/psychiatric behaviors and the molecular mechanisms. We found that mice with GSK-3β deletion in DG excitatory neurons displayed spatial and fear memory defects with an anti-anxiety behavior. Further studies demonstrated that GSK-3β deletion in DG subset inhibited hippocampal synaptic transmission and reduced levels of GluN1, GluN2A and GluN2B (NMDAR subunits), GluA1 (AMPAR subunit), PSD93 and drebrin (postsynaptic structural proteins), and synaptophysin (presynaptic protein). GSK-3β deletion also suppressed the activity-dependent neural activation and calcium/calmodulin-dependent protein kinase II (CaMKII)/CaMKIV-cAMP response element binding protein (CREB) signaling. Our data suggest that GSK-3β in hippocampal DG excitatory neurons is essential for maintaining synaptic plasticity and memory.
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http://dx.doi.org/10.1038/s41598-017-06173-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515925PMC
July 2017