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1.
Dev Comp Immunol ; 102: 103489, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31473266

RESUMO

The Canine Distemper Virus (CDV) is a high fatal virus to the giant panda (Ailuropoda melanoleuca), where CDV vaccination is a key preventative measure in captive giant pandas. However, the immune response of giant pandas to CDV vaccination has been little studied. In this study, we investigated the blood transcriptome expression profiles of five giant panda cubs after three inoculations, 21 days apart. Blood samples were collected before vaccination (0 Day), and 24 h after each of the three inoculations; defined here as 1 Day, 21  Day, and 42  Day. Compared to 0 Day, we obtained 1262 differentially expressed genes (DEGs) during inoculations. GO and KEGG pathways enrichment analysis of these DEGs found 222 GO terms and 40 pathways. The maximum immune-related terms were enriched by DEGs from comparisons of 21  Day and 0 Day. In the PPI analysis, we identified RSAD2, IL18, ISG15 immune-related hub genes from 1 Day and 21 Day comparison. Compared to 0 Day, innate immune-related genes, TLR4 and TLR8, were up-regulated at 1 Day, and the expressions of IRF1, RSAD2, MX1, and OAS2 were highest at 21  Day. Of the adaptive immune-related genes, IL15, promoting T cell differentiation into CD8+T cells, was up-regulated after the first two inoculations, IL12ß, promoting T cell differentiation into memory cells, and IL10, promoting B cell proliferation and differentiation, were down-regulated during three inoculations. Our results indicated that the immune response of five giant panda cubs was strongest after the second inoculation, most likely protected against CDV infection through innate immunity and T cells, but did not produce enough memory cells to maintain long-term immunity after CDV vaccination.

2.
Food Microbiol ; 86: 103342, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31703884

RESUMO

As the spirit of Chinese Sichuan cuisine, Pixian Doubanjiang (DBJ) is an indispensable flavor condiment and has been widely used for centuries, which is made from red pepper (Capsicum annuum L.), meju and brine after open ripening fermentation. In this study, the physicochemical factors including pH value, titratable acidity, moisture, organic acids, free amino acids and volatile components etc., were identified; the compositions of microbial communities and representative microbiota were investigated; the correlations between physicochemical factors and representative microbial taxa were analyzed, at different ripening stages. The results indicated that the organic acids were all relatively stable starting from the 12th month; most of the free amino acids (17/20) reached the peak concentrations at the 6th month and 28 volatile components were considered as major odorant flavors in DBJ. Zygosaccharomyces rouxii could be the key microorganism associated with 10 volatile components to the maturing of DBJ flavor. The comprehensive analysis on the physicochemical changes related to the succession of microbiota is expected to help us understand the maturing of the taste and flavor in DBJ production.

3.
J Affect Disord ; 260: 91-96, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31493645

RESUMO

BACKGROUND: Major depressive disorder (MDD) patients with comorbid anxiety symptoms showed obvious cognitive deficits. However, it remains unclear whether comorbid anxiety symptoms will make a specific contribution to cognitive deficits in MDD. METHODS: Executive function, processing speed, attention and memory were assessed in 162 MDD patients, and 142 healthy controls (HCs) by a comprehensive neuropsychological battery. 14-item Hamilton Anxiety Rating Scale (HAM-A) was used for anxiety symptoms and MDD patients with HAM-A total score >14 were classified into MDD with comorbid anxiety (MDDA) group. A multivariate analysis of covariance and regression models was conducted to evaluate the effects of anxiety symptoms on cognitive deficits. RESULTS: There were no significantly differences in all 4 cognitive domains between MDD alone and MDDA patients (all p < 0.05). In MDDA subgroup, HAM-A total score contributed to executive function and memory (both p < 0.05), while HAM-A psychic symptoms contributed to all 4 domains (all p < 0.05). Moreover, after controlling for the severity of depression, either anxiety symptoms shown as HAMA total score or psychic anxiety symptoms only contributed significantly to the executive function performance. LIMITATIONS: The cross-sectional design made it hard to acquire a cognitive performance trajectory accompanied by the fluctuations in anxiety symptoms. CONCLUSION: Our findings suggest that there is no significant difference in cognitive performance between MDD alone and MDDA patients. However, comorbid anxiety, especially psychic anxiety may contribute to extensive cognitive deficits in MDDA patients. Notably, anxiety symptoms only independently triggered executive dysfunction when eliminating effect of the severity of depression.

4.
Bioresour Technol ; 294: 122183, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31683455

RESUMO

Sewage nitritation is a promising process for nitrogen removal, but its practical application is limited by long start-up period and unstable operation. In this study, hydroxylamine (NH2OH) addition and real-time aeration control strategies were adopted for the promotion of sewage nitritation in a sequencing batch reactor. Initially, 4.5 mg/L NH2OH was added into reactor every 24 h to establish nitritation, increasing the nitrite accumulation ratio (NAR) from 1.7% to 93% in 19 d. In the following period, NH2OH addition was stopped and nitritation remained stable over 55 d, with NAR of 97% by real-time aeration control. The aeration duration was determined by characteristic points on pH curve. The main genera of nitrite oxidizing bacteria, Nitrobacter and Nitrospira, were both eliminated from the system, supporting the long-term stability of nitritation. Overall, NH2OH addition and real-time aeration control is an excellent strategy for establishing and maintaining effective sewage nitritation.


Assuntos
Reatores Biológicos , Esgotos , Hidroxilamina , Hidroxilaminas , Nitritos , Nitrogênio , Oxirredução
5.
Transgenic Res ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673914

RESUMO

The vitamin E family includes tocopherols and tocotrienols, which are essential lipid-soluble antioxidants necessary for human and livestock health. The seeds of many plant species, including maize, have high gamma (γ)-tocopherol but low alpha (α)-tocopherol contents; however, α-tocopherol is the most effective antioxidant. Therefore, it is necessary to optimize the tocopherol composition in plants. α-Tocopherol is synthesized from γ-tocopherol by γ-tocopherol methyltransferase (γ-TMT, VTE4) in the final step of the tocopherol biosynthetic pathway. In the present study, the full-length coding sequence (CDS) of γ-TMT was isolated from Zea mays, named ZmTMT. The ZmTMT CDS was 1059 bp in size, encoding 352 amino acids. Recombinant ZmTMT was expressed in Escherichia coli and the purified protein effectively converted γ-tocopherol into α-tocopherol in vitro. A comparison of enzyme activities showed that the activity of ZmTMT was higher than that of GmTMT2a (Glycine max) and AtTMT (Arabidopsis thaliana). Overexpression of ZmTMT increased the α-tocopherol content 4-5-fold in transgenic Arabidopsis and around 6.5-fold in transgenic maize kernels, and increased the α-/γ-tocopherol ratio to approximately 15 and 17, respectively. These results show that it is feasible to overexpress ZmTMT to optimize the tocopherol composition in maize; such a corn product might be useful in the feed industry in the near future.

6.
Nat Commun ; 10(1): 4959, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672968

RESUMO

Tight control of centriole duplication is critical for normal chromosome segregation and the maintenance of genomic stability. Polo-like kinase 4 (Plk4) is a key regulator of centriole biogenesis. How Plk4 dynamically promotes its symmetry-breaking relocalization and achieves its procentriole-assembly state remains unknown. Here we show that Plk4 is a unique kinase that utilizes its autophosphorylated noncatalytic cryptic polo-box (CPB) to phase separate and generate a nanoscale spherical condensate. Analyses of the crystal structure of a phospho-mimicking, condensation-proficient CPB mutant reveal that a disordered loop at the CPB PB2-tip region is critically required for Plk4 to generate condensates and induce procentriole assembly. CPB phosphorylation also promotes Plk4's dissociation from the Cep152 tether while binding to downstream STIL, thus allowing Plk4 condensate to serve as an assembling body for centriole biogenesis. This study uncovers the mechanism underlying Plk4 activation and may offer strategies for anti-Plk4 intervention against genomic instability and cancer.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31670455

RESUMO

Photocatalytic overall water splitting has been recognized as a promising approach to convert solar energy into hydrogen. However, most of the photocatalysts suffer from low efficiencies mainly due to the poor charge separation property. Herein, taking a model semiconductor gallium nitride (GaN) as an example, we uncovered that photogenerated electrons and holes can be spatially separated to the nonpolar and polar surfaces of GaN nanorod arrays, which is presumably ascribed to the different surface band bending induced by the surface polarity. The photogenerated charge separation efficiency of GaN can be enhanced significantly from ~8% to more than 80% via co-exposing polar and nonpolar surfaces. Furthermore, spatially assembling of reduction and oxidation cocatalysts selectively on the nonpolar and polar surfaces remarkably boosts photocatalytic overall water splitting, with the quantum efficiency increased from 0.9% for the film photocatalyst to 6.9% for the nanorod arrays photocatalyst.

8.
Int J Nanomedicine ; 14: 8499-8507, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695377

RESUMO

Background: Beyond magnetic resonance imaging (MRI), which has been widely used clinically, molecular MRI (mMRI) can further provide qualitative and quantitative information at the cellular and molecular levels. However, the diagnostic accuracy may not be satisfactory via single-contrast mMRI due to some interferences in vivo. T1/T2 dual-contrast MRI using the same contrast agent (CA) could significantly improve the detection accuracy. Therefore, in this study, we fabricated poly(ethylene glycol) (PEG)-coated, manganese-doped iron oxide nanocomposites (Mn-IONPs@PEG) as T1/T2 dual-contrast CA, and evaluated its feasibility of T1/T2 dual-contrast MRI in vitro and in vivo. Methods: Mn-IONPs were prepared by the thermal decomposition of iron-eruciate and manganese-oleate complexes and were coated with 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy[polyethylene glycol]-2000) (DSPE-PEG 2000). The physicochemical properties and cytotoxicity of the Mn-IONPs were fully characterized, followed by MRI in vitro and in vivo. Results: Ultrasmall 3 nm-sized nanoparticles were successfully prepared and were identified using transmission electron microscopy (TEM), high-resolution TEM, and X-ray diffraction. After coating with DSPE-PEG, the Mn-IONPs@PEG displayed excellent hydrophilicity and good biocompatibility. Due to the manganese-doping and PEG coating, the Mn-IONPs@PEG showed good relaxivity in vitro. Especially, the Mn-IONPs@PEG coated with DSPE-PEG following a mass ratio to Mn-IONPs of 1:20 showed harmonious longitudinal relaxivity (r 1 = 7.1 mM-1s-1) and transversal relaxivity (r 2 = 120.9 mM-1s-1), making it a better candidate for T1/T2 dual-contrast mMRI. After administrated via a caudal vein, the Mn-IONPs@PEG can induce significant enhancement in both T1-weighted and T2-weighted MR images and the time at 10 mins after injection was regarded as a suitable time for imaging because both the T1 and T2 enhancement were optimum at that time. Conclusion: The obtained Mn-IONPs@PEG exhibited good r 1 and r 2 and was a reasonable candidate for T1/T2 dual-contrast mMRI.

9.
Mol Med Rep ; 20(6): 4867-4874, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31702808

RESUMO

Hyperoxia may cause pulmonary fibrosis in neonates and is characterized by the epithelial­to­mesenchymal transition (EMT) of alveolar epithelial cells. The placental growth factor (PLGF) gene is a member of the vascular endothelial growth factor family and is highly expressed in lung tissues that have been exposed to hyperoxia. The aim of the present study was to assess the role of PLGF in the EMT of lung tissue. Lung tissue exhibiting low PLGF expression was obtained by injecting rats exposed to hyperoxia with a PLGF­silencing lentiviral plasmid. Western blot analysis and immunohistochemistry revealed that expression levels of the EMT­related protein epithelial­cadherin were increased, whereas its inhibitor protein zinc­finger E­box binding homeobox 2 was decreased in these rats. These data demonstrated that PLGF silencing may significantly mitigate hyperoxia­induced EMT in rat lung tissue. Additionally, an increase in phosphorylated­p38 MAPK protein expression indicated that PLGF may be able to regulate hyperoxia­induced lung injury in rats via the p38 MAPK pathway.

10.
Water Res ; 169: 115084, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31669906

RESUMO

Elemental sulfur-driven autotrophic denitrification (SADN) is a cost-effective approach for treating secondary effluent from wastewater treatment plants (WWTPs). Additional organics are generally supplemented to promote total nitrogen (TN) removal, reduce nitrite accumulation and sulfate production, and balance the pH decrease induced by SADN. However, understanding of the impacts of organic supplementation on microbial communities, nitrogen metabolism, denitrifier activity, and SADN rates in sulfur-based denitrification reactors is still limited. Here, a sulfur-based denitrification reactor was continuously operated for 272 days during which six different C/N ratios were tested successively (2.7, 1.5, 0.7, 0.5, 0.25, and 0). Organic supplementation improved TN removal and decreased NO2- accumulation, but reduced the relative abundance of denitrifiers and the contribution of autotrophic nitrate-reducing bacteria (aNRB) to TN removal during the long-term operation of reactor. Predictive functional profiling showed that nitrogen metabolism potential increased with decreasing C/N ratios. SADN was the predominant removal process when the C/N ratio was ≤0.7 (achieving 60% contribution when C/N = 0.7). Although organic supplementation weakened the dominant role of aNRB in denitrification, batch tests for the first time demonstrated that it could accelerate the SADN rate, attributed to the improvement of sulfur bioavailability, likely via the formation of polysulfide. A possible nitrogen removal pathway with multiple electron donors (i.e., sulfur, organics, sulfide, and polysulfide) in a sulfur-based denitrification reactor with organic supplementation was therefore proposed. However, supplementation with a high level of organics could increase the operational cost and effluent concentrations of sulfide and organics as well as enrich heterotrophic denitrifiers. Moreover, microbial community had substantial changes at C/N ratios of >0.5. Accordingly, an optimal C/N ratio of 0.25-0.5 was suggested, which could simultaneously minimize the additional operating cost associated with organic supplementation and maximize TN removal and SADN rates.

11.
Mol Ther Nucleic Acids ; 18: 627-637, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31689617

RESUMO

Despite surgery and adjuvant therapy, early-stage lung adenocarcinoma (LUAD) treatment often fails due to local or metastatic recurrence. However, the mechanism is largely unknown. Here, we report that increased expression levels of miR-134-5p and decreased levels of disabled-2 (DAB2) were significantly correlated with recurrence in stage I LUAD patients. Our data show that miR-134-5p overexpression or DAB2 silencing strongly stimulated LUAD cell metastasis and chemoresistance. In contrast, inhibition of miR-134-5p or overexpression of DAB2 strongly suppressed LUAD cell metastasis and overcame the insensitivity of chemoresistant LUAD cells to chemotherapy. In addition, we demonstrated that DAB2 is a target of miR-134-5p and that miR-134-5p stimulates chemoresistance and metastasis through DAB2 in LUAD. Taken together, these findings suggest that miR-134-5p and its target gene DAB2 have potential as a biomarker for predicting recurrence in stage I LUAD patients. Additionally, miR-134-5p inhibition or DAB2 restoration may be a novel strategy for inhibiting LUAD metastasis and overcoming LUAD cell resistance to chemotherapy.

12.
Pharmacology ; : 1-9, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694038

RESUMO

OBJECTIVES: (1) To detect the whether the effects of simulated ischemia on INa of rat left ventricular myocytes in a time-dependent manner and the effects of atorvastatin on ischemia INa; (2) To investigate the effects of atorvastatin on INa of rat-simulated ischemia/reperfusion (I/R) ventricular cells. MATERIALS AND METHODS: Ventricular cells were enzymatically isolated by Langendorff perfusion system. Whole-cell patch clamp was applied to detect INa level. Some elements of extracellular fluid were hanged to simulate the status of normal, I and R condition. Then the effects of atorvastatin on INa were observed. RESULTS: (1) During simulated reperfusion, INa decreased and atorvastatin further suppressed the reduction degree. (2) At test potential -40 mV, no difference was detected among peak INa amplitude of ischemia for 20 min, reperfusion phase 3/5/7/9 min in continuous ischemia (I) group (p = 0.275). In I/R group, peak INa amplitude continuously decreased at 3 min (p = 0.005) and 9 min (p = 0.041). In atorvastatin intervention + I/R (Statin + I/R) group, peak INa amplitude at reperfusion 3 min decreased compared with ischemia phase (p = 0.000), while no significant difference was detected between 3 and 9 min (p = 0.858). The differences were significant at the same time point between groups. At reperfusion 3/5/7/9 min, peak INa of the I/R group was lower than the ischemia group (all p = 0.000), same as the Statin + I/R group (p = 0.000, p = 0.003, p = 0.006, and p = 0.001). Peak INa of the Statin + I/R group was higher than the I/R group at the same time point (p = 0.011, p = 0.033, p = 0.003, p = 0.003). There was no change in the I group during reperfusion phase (p > 0.05). In I/R group, V1/2 (mV) shifted from -58.87 ± 3.36 to -54.33 ± 2.40, k (mV) shifted from 1.25 ± 0.59 to 1.91 ± 0.84 (p < 0.05). In the Statin + I/R group, V1/2 (mV) increased from -57.80 ± 2.97 to -52.76 ± 3.14 (p < 0.01), no change was observed in k (p > 0.05). CONCLUSIONS: (1) In the status of reperfusion, INa decreased more than that in the status of ischemia. (2) Atorvastatin protected the cells from reduction of INa during long-time simulated (>15 min) I/R. (3) Overall, atorvastatin affected INa of the normal, simulated ischemic/reperfusion cell in rat left ventricle by blocking sodium channel -directly.

13.
Doc Ophthalmol ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31720980

RESUMO

PURPOSE: To investigate the accuracy of the RETeval full-field flicker ERG in the screening of diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) and to determine a suitable range of DR diagnostic reference for patients with type 2 diabetes mellitus (T2DM). METHODS: This was a cross-sectional study involving 172 subjects with T2DM, including 71 subjects without clinically detectable DR (NDR), 25 subjects with mild non-proliferative diabetic retinopathy (NPDR), 24 subjects with moderate NPDR, 27 subjects with severe NPDR and 25 subjects with proliferative diabetic retinopathy (PDR). All the subjects underwent a full-field flicker ERG using the RETeval device (DR assessment protocol), which is a mydriasis-free, full-field electroretinogram (ERG) recording system. The performance of the DR assessment protocol in detecting the DR (including mild NPDR, moderate NPDR, severe NPDR and PDR) and VTDR was analyzed with the receiver operating characteristic (ROC) curve. RESULTS: For the detection of DR (mild NPDR, moderate NPDR, severe NPDR, PDR), the area under the ROC curve was 0.867 (p < 0.001, 95% CI 0.814-0.920), and the best cutoff value for DR was determined to be 20.75, with a sensitivity of 80.2% and specificity of 81.7%. Meanwhile, for the detection of VTDR, the area under the ROC curve was 0.965 (p < 0.001, 95% CI 0.941-0.989), and the best cutoff value was set to 23.05, with a sensitivity of 94.6% and a specificity of 88.8%. CONCLUSION: The DR assessment protocol in RETeval device was effective in screening for DR (mild NPDR, moderate NPDR, severe NPDR, PDR) and VTDR in patients with diabetes. It could be helpful in referring and managing patients with T2DM in primary healthcare setting. However, caution should be taken that optimal cutoff value of DR assessment protocol may vary in different ethnic populations.

14.
J Food Sci ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31721214

RESUMO

This work aimed to investigate the phytochemical composition, nutritional value, antioxidant, antihemolytic, antihyperglycemic, and antiproliferative activities of flaxleaf fleabane (Conyza bonariensis) leaves. Different concentrations of water and ethanol (0:100, 25:75, 50:50, 75:25, and 100:0 v/v) were used in the extraction process and results showed that the hydroalcoholic extract (50:50 v/v) presented the highest total phenolics, ortho-diphenolics, Folin-Ciocalteu reducing capacity, FRAP, and Fe2+ chelating ability values. Flaxleaf fleabane leaves (FFL) contained 19.6 g/100 g of fibers and 26 g/100 g of proteins. Ellagic acid, procyanidin A2, caffeic, rosmarinic, gallic, and 2,5-dihydroxybenzoic acids were the main phenolics. This phenolic-rich extract inhibited the lipid oxidation of Wistar rat brain (IC50 = 863.0 mg GAE/L), inhibited α-glucosidase activity (IC50 = 435.4 µg/mL), protected human erythrocytes against mechanical hemolysis at different osmolarity conditions, and showed cytotoxic/antiproliferative effects against human ileocecal adenocarcinoma cells (HCT8; IC50 = 552.6 µg/mL) but no cytotoxicity toward noncancerous human lung fibroblast (IMR90). Overall, FFL showed potential to be explored by food companies to be a source of proteins, natural color substances, and phenolic compounds. PRACTICAL APPLICATION: Flaxleaf fleabane leaves (FFL) are usually burnt or partially given to cattle, without a proper utilization as a source of nutrients for human nutrition. Here, we studied the nutritional composition, phenolic composition, and toxicological aspects of FFL using different biological protocols. FFL was proven to be a rich source of proteins and dietary fibers and showed antioxidant activity measured by chemical and in vitro biological assays. Additionally, as it did protected human red cells and did not show cytotoxicity, we assume FFL has relative safety to be consumed as a nonconventional edible plant.

15.
Chemistry ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31721326

RESUMO

Design and synthesis of non-invasive theranostics that integrate the advantages of multimodality imaging and therapeutics exhibits great prospect in biomedical field. Herein, a novel nanohybrid based on Bi 2 Se 3 -conjugated upconversion nanoparticles (UCNPs) has been successfully developed through a simple in situ growth strategy. Under the 808 nm near infrared (NIR) laser irradiation, the UCNPs can emit bright visible light, whereas the Bi 2 Se 3 nanomaterial exhibits efficient photothermal conversion capacity. Moreover, the as-synthesized UCNPs-Bi 2 Se 3 nanohybrid exhibits efficient cell upconversion luminescence (UCL), reasonable CT imaging, and admirable cancer cells ablation capacities, which further emphasizes the efficiency to conduct UCL imaging and photothermal therapy simutaneously by this strategy. The designed theranostic strategy guided by dual modal imaging endowed with real-time dynamic monitoring, remote controllability and non-invasiveness, making UCNPs-Bi 2 Se 3 nanohybrid as ideal candidates for non-invasive multimodal imaging-guided photothermal therapy towards precise diagnosis and treatment of cancer.

16.
J Am Chem Soc ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31644285

RESUMO

Lysine lipoylation, a highly conserved lysine post-translational modification, plays a critical role in regulating cell metabolism. The catalytic activity of a number of vital metabolic proteins, such as pyruvate dehydrogenase (PDH), depends on lysine lipoylation. Despite its important roles, the detailed biological regulatory mechanism of lysine lipoylation remains largely unexplored. Herein we designed a powerful affinity-based probe, KPlip, to interrogate the interactions of lipoylated peptide/proteins under native cellular environment. Large-scale chemical proteomics analysis revealed a number of binding proteins of KPlip, including sirtuin 2 (Sirt2), an NAD+-dependent protein deacylase. To explore the potential activity of Sirt2 toward lysine lipoylation, we designed a single-step fluorogenic probe, KTlip, which reports delipoylation activity in a continuous manner. The results showed that Sirt2 led to significant delipoylation of KTlip, displaying up to a 60-fold fluorescence increase in the assay. Further kinetic experiments with different peptide substrates revealed that Sirt2 can catalyze the delipoylation of peptide (DLAT-PDH, K259) with a remarkable catalytic efficiency (kcat/Km) of 3.26 × 103 s-1 M-1. The activity is about 400-fold higher than that of Sirt4, the only mammalian enzyme with known delipoylation activity. Furthermore, overexpression and silencing experiments demonstrated that Sirt2 regulates the lipoylation level and the activity of endogenous PDH, thus unequivocally confirming that PDH is a genuine physiological substrate of Sirt2. Using our chemical probes, we have successfully established the relationship between Sirt2 and lysine lipoylation in living cells for the first time. We envision that such chemical probes will serve as useful tools for delineating the roles of lysine lipoylation in biology and diseases.

17.
Chem Rec ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573147

RESUMO

The development of versatile catalyst systems and new transformations for the utilization of carbon dioxide (CO2 ) is of great interest and significance. This Personal Account reviews our studies on the exploration of the reactions of CO2 with various substrates by the use of N-heterocyclic carbene (NHC)-copper catalysts. The carboxylation of organoboron compounds gave access to a wide range of carboxylic acids with excellent functional group tolerance. The C-H bond carboxylation with CO2 emerged as a straightforward protocol for the preparation of a series of aromatic carboxylic esters and butenoates from simple substrates. The hydrosilylation of CO2 with hydrosilanes provided an efficient method for the synthesis of silyl formate on gram scale. The hydrogenative or alkylative carboxylation of alkynes, ynamides and allenamides yielded useful α,ß-unsaturated carboxylic acids and α,ß-dehydro amino acid esters. The boracarboxylation of alkynes or aldehydes afforded the novel lithium cyclic boralactone or boracarbonate products, respectively. The NHC-copper catalysts generally featured excellent functional group compatibility, broad substrate scope, high efficiency, and high regio- and stereoselectivity. The unique electronic and steric properties of the NHC-copper units also enabled the isolation and structural characterization of some key intermediates for better understanding of the catalytic reaction mechanisms.

18.
Phys Rev Lett ; 123(10): 106001, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31573276

RESUMO

State-to-state scattering dynamics of H_{2}O from Cu(111) has been studied by a fully coupled quantum mechanical model which explicitly accounts for the most important molecular degrees of freedom, based on a first-principles determined potential energy surface. When H_{2}O in its antisymmetric O-H stretching vibration (ν_{3}) collides with the surface, we find that the intramolecular vibrational energy redistribution (IVR) is predominant from ν_{3} to the symmetric stretching mode (ν_{1}), while rather inefficient to the bending mode (ν_{2}). This mode-specific IVR results from the strong couplings between stretching modes, which equally dispose the initial energy in ν_{3} into local stretching modes differing by a phase factor. Given the number of stretching modes in H_{2}O and CH_{4}, this mechanism naturally explains why the product ν_{1}/ν_{3} ratio calculated here is ∼3 times over that recently measured for CH_{4} scattering on Ni(111), suggesting that the nonstatistical IVR is more general than expected in polyatomic molecules.

19.
ACS Appl Mater Interfaces ; 11(44): 41304-41312, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31603303

RESUMO

The ever-increasing demand for large-scale energy storage has driven the prosperous investigation of sodium-ion batteries (NIBs). As a promising cathode candidate for NIBs, P2-type Na2/3Ni1/3Mn2/3O2 (NaNMO), a prototype sodium-layered oxide, has attracted extensive attention because of its high operating voltage and high capacity density. Although its electrochemical properties have been extensively investigated, the fundamental charge compensation mechanism, that is, the cationic and anionic redox reactions, is still elusive. In this report, we have systematically investigated the transition metal and oxygen redox reactions of NaNMO nanoflakes using bulk-sensitive soft X-ray absorption spectroscopy and full-range mapping of resonant inelastic X-ray scattering from an atomic-level view. We show that the bulk Mn3+/Mn4+ redox couple emerges from the first discharge process with the increment of inactive Mn3+ upon cycling, which may have a negative effect on the cyclability. In contrast, the bulk Ni redox mainly stems from the Ni2+/Ni3+ redox couple, in contrast to the conventional wisdom of the Ni2+/Ni4+ redox couple. The quantitative analysis provides unambiguous evidence for the continuous reduction of the average valence state of Mn and Ni over extended cycles, leading to the voltage fading. In addition, we reveal that the oxygen anions also participate in the charge compensation process mainly through irreversible oxygen release rather than reversible lattice oxygen redox. Such understanding is vital for the precise design and optimization of NaNMO electrodes for rechargeable NIBs with outstanding performance.

20.
Med Sci Monit ; 25: 7694-7701, 2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31606729

RESUMO

BACKGROUND Alprostadil can inhibit inflammation and reduce inflammation-related injury in many inflammatory diseases. However, the anti-inflammatory effect of alprostadil in decreasing acute pancreatitis (AP) injury remains unknow. This study aimed to investigate the possible protective effects and mechanism of alprostadil against AP in rats. MATERIAL AND METHODS Forty healthy Sprague­Dawley rats were randomly divided into a control group, an AP group, an AP-alprostadil group, an AP-AG490 group, and an AP-(alprostadil+AG490) group. An animal model of acute pancreatitis was established. The pathological changes of the pancreases in each group were observed. We assessed levels of malondialdehyde (MDA), superoxide dismutase (SOD), and myeloperoxidase (MPO), as well as serum IL-1ß, IL-6, IL-10, and TNF-alpha. TUNEL assay was used to detect apoptosis of pancreatic cells. The proteins p-Jak2 and p-Stat3 were investigated by Western blot. RESULTS Compared with the control group, pancreatic pathological score, pancreatic apoptosis, MDA, MPO, serum IL-1ß, IL-6, and TNF-alpha levels were significantly higher in the AP group, and SOD levels were significantly decreased. Compared with the AP group, after treatment with alprostadil, AG490, and alprostadil+AG490, respectively, the pancreatic pathological score, apoptosis, MDA, MPO, serum IL-1ß, IL-6, and TNF-alpha were significantly decreased in AP rats, while SOD levels were significantly increased. The protein levels of p-JAK2 and p-STAT3 were significantly upregulated in the AP group compared with the control group, and the protein levels of p-JAK2 and p-STAT3 after treatment with alprostadil, AG490, and alprostadil+AG490 were significantly decreased, and the effect of alprostadil+AG490 was the strongest. CONCLUSIONS Alprostadil can reduce pancreatic tissue damage, delay pancreatic cell apoptosis, and reduce inflammation and anti-oxidative stress by inhibiting the JAK2/STAT3 signal pathway, thus protecting the pancreas.

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