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1.
Huan Jing Ke Xue ; 44(4): 1801-1810, 2023 Apr 08.
Article in Chinese | MEDLINE | ID: mdl-37040931

ABSTRACT

Meteorological conditions have important impacts on surface ozone (O3) formation. To evaluate the influence of future climate change on O3 concentrations in different regions of China, this study employed the climate data from the community earth system model provided by the CMIP5 under the RCP4.5, RCP6.0, and RCP8.5 scenarios to generate the initial and boundary conditions for the WRF model. Then, the dynamic downscaling WRF results were fed into a CMAQ model as meteorological fields with fixed emission data. Two 10-year periods (2006-2015 and 2046-2055) were selected in this study to discuss the impacts of climate change on O3. The results showed that climate change increased boundary layer height, mean temperature, and heatwave days in China during summer. Relative humidity decreased and wind speed near the surface showed no obvious change in the future. O3 concentration showed an increasing trend in Beijing-Tianjin-Hebei, Sichuan Basin, and South China. The extreme value of O3 maximum daily 8-hour moving average (MDA8) showed an increasing trend, following the order of RCP8.5 (0.7 µg·m-3)>RCP6.0 (0.3 µg·m-3)>RCP4.5 (0.2 µg·m-3). The number of days exceeding the standard for summer O3 had a similar spatial distribution with the heatwave days in China. The increase in heatwave days led to the increase in O3 extreme pollution events, and the possibility of a long-lasting O3 pollution event will increase in China in the future.

2.
J Mater Chem A Mater ; 11(10): 5083-5094, 2023 Mar 07.
Article in English | MEDLINE | ID: mdl-36911161

ABSTRACT

The application of gas diffusion electrodes (GDEs) for the electrochemical reduction of CO2 to value-added products creates the possibility of achieving current densities of a few hundred mA cm-2. To achieve stable operation at such high reaction rates remains, however, a challenging task, due to the flooding of the GDE. In order to mitigate flooding in a zero-gap membrane-electrode assembly (MEA) configuration, paths for effective electrolyte perspiration inside the GDE structure have to be kept open during the electrolysis process. Here we demonstrate that apart from the operational parameters of the electrolysis and the structural properties of the supporting gas diffusion layers, also the chemical composition of the applied catalyst inks can play a decisive role in the electrolyte management of GDEs used for CO2 electroreduction. In particular, the presence of excess amounts of polymeric capping agents (used to stabilize the catalyst nanoparticles) can lead to a blockage of micropores, which hinders perspiration and initiates the flooding of the microporous layer. Here we use a novel ICP-MS analysis-based approach to quantitatively monitor the amount of perspired electrolyte that exits a GDE-based CO2 electrolyser, and we show a direct correlation between the break-down of effective perspiration and the appearance of flooding-the latter ultimately leading to a loss of electrolyser stability. We recommend the use of an ultracentrifugation-based approach by which catalyst inks containing no excess amount of polymeric capping agents can be formulated. Using these inks, the stability of electrolyses can be ensured for much longer times.

3.
Small ; 19(6): e2205012, 2023 02.
Article in English | MEDLINE | ID: mdl-36398653

ABSTRACT

The fluid-filled cystic cavity sealed by a dense scar developed following traumatic spinal cord injury (SCI) has been a major obstacle to neural regeneration and functional recovery. Here the transected lesion is bridged using a functional self-assembling peptide (F-SAP) hydrogel loaded with membrane-permeable intracellular sigma peptide (ISP) and intracellular LAR peptide (ILP), targeted at perturbing chondroitin sulfate proteoglycan (CSPG) inhibitory signaling. As compared to F-SAP hydrogel loaded with chondroitinase ABC, the F-SAP+ISP/ILP promotes a beneficial anti-inflammatory response via manipulation of microglia/macrophages infiltration and assembly of extracellular matrix (ECM) molecules into fibrotic matrix rather than scarring tissues. The remodeled ECM creates a permissive environment that supports axon regrowth and the formation of synaptic connections with neurons derived from endogenous neural stem cells. The remodeled networks contribute to functional recovery, as demonstrated by improved hind limb movements and electrophysiological properties. This work proposes a unique mechanism that ECM remodeling induced by CSPG-manipulation-based anti-inflammation can construct a permissive environment for neural regeneration, and shed light on the advancement of manipulation of cascading cellular and molecular events potential for endogenous repair of SCI.


Subject(s)
Neural Stem Cells , Spinal Cord Injuries , Humans , Chondroitin Sulfate Proteoglycans , Neurons/physiology , Axons , Cicatrix
4.
Small Methods ; 6(9): e2200369, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35810472

ABSTRACT

The advantage of employing gas diffusion electrodes (GDEs) in carbon dioxide reduction electrolyzers is that they allow CO2 to reach the catalyst in gaseous state, enabling current densities that are orders of magnitude larger than what is achievable in standard H-type cells. The gain in the reaction rate comes, however, at the cost of stability issues related to flooding that occurs when excess electrolyte permeates the micropores of the GDE, effectively blocking the access of CO2 to the catalyst. For electrolyzers operated with alkaline electrolytes, flooding leaves clear traces within the GDE in the form of precipitated potassium (hydrogen)carbonates. By analyzing the amount and distribution of precipitates, and by quantifying potassium salts transported through the GDE during operation (electrolyte perspiration), important information can be gained with regard to the extent and means of flooding. In this work, a novel combination of energy dispersive X-ray and inductively coupled plasma mass spectrometry based methods is employed to study flooding-related phenomena in GDEs differing in the abundance of cracks in the microporous layer. It is concluded that cracks play an important role in the electrolyte management of CO2 electrolyzers, and that electrolyte perspiration through cracks is paramount in avoiding flooding-related performance drops.

5.
J Control Release ; 343: 482-491, 2022 03.
Article in English | MEDLINE | ID: mdl-35134461

ABSTRACT

Various extracellular factors jointly control a wide variety of neuronal functions. On-demand delivery system provides a platform to integrate multiple signals in one intervention. In this study, we fabricated an electrically controlled drug delivery nanocomposite composed of graphene oxide (GO) deposited inside a poly(3,4-ethylenedioxythiophene) (PEDOT) film. 7,8-dihydroxyflavone (7,8-DHF) was loaded on GO via π-π stacking and consequentially encapsulated into the electrochemically active film during deposition, which was followed by a Dopamine-graft-Chitosan (CD) coating to improve the biocompatibility. 7,8-DHF was released in response to voltage stimulation and the dosage was adjusted by altering the magnitude of stimulation. The on-demand delivery system promoted dorsal root ganglion (DRG) neurite outgrowth, Schwann cell migration, myelination, and synapse transmission. Neuronal mitochondrial biogenesis was enhanced as determined by immunofluorescence staining and gene expression of HSP60, a mitochondrial localized quality control protein. Therefore, we provided an on-demand delivery platform of temporal control and dosage flexibility to integrate multiple signals in the modulation of neural behaviors and functions.


Subject(s)
Nanocomposites , Schwann Cells , Cell Communication , Ganglia, Spinal , Neurons
6.
Theranostics ; 11(20): 10125-10147, 2021.
Article in English | MEDLINE | ID: mdl-34815808

ABSTRACT

Background: Fibroblast growth factor receptors (FGFRs) are key targets for nerve regeneration and repair. The therapeutic effect of exogenous recombinant FGFs in vivo is limited due to their high molecular weight. Small peptides with low molecular weight, easy diffusion, low immunogenicity, and nontoxic metabolite formation are potential candidates. The present study aimed to develop a novel low-molecular-weight peptide agonist of FGFR to promote nerve injury repair. Methods: Phage display technology was employed to screen peptide ligands targeting FGFR2. The peptide ligand affinity for FGFRs was detected by isothermal titration calorimetry. Structural biology-based computer virtual analysis was used to characterize the interaction between the peptide ligand and FGFR2. The peptide ligand effect on axon growth, regeneration, and behavioral recovery of sensory neurons was determined in the primary culture of sensory neurons and dorsal root ganglia (DRG) explants in vitro and a rat spinal dorsal root injury (DRI) model in vivo. The peptide ligand binding to other membrane receptors was characterized by surface plasmon resonance (SPR) and liquid chromatography-mass spectrometry (LC-MS)/MS. Intracellular signaling pathways primarily affected by the peptide ligand were characterized by phosphoproteomics, and related pathways were verified using specific inhibitors. Results: We identified a novel FGFR-targeting small peptide, CH02, with seven amino acid residues. CH02 activated FGFR signaling through high-affinity binding with the extracellular segment of FGFRs and also had an affinity for several receptor tyrosine kinase (RTK) family members, including VEGFR2. In sensory neurons cultured in vitro, CH02 maintained the survival of neurons and promoted axon growth. Simultaneously, CH02 robustly enhanced nerve regeneration and sensory-motor behavioral recovery after DRI in rats. CH02-induced activation of FGFR signaling promoted nerve regeneration primarily via AKT and ERK signaling downstream of FGFRs. Activation of mTOR downstream of AKT signaling augmented axon growth potential in response to CH02. Conclusion: Our study revealed the significant therapeutic effect of CH02 on strengthening nerve regeneration and suggested a strategy for treating peripheral and central nervous system injuries.


Subject(s)
Peptides/pharmacology , Receptors, Fibroblast Growth Factor/metabolism , Spinal Nerve Roots/drug effects , Animals , Axons/metabolism , Cells, Cultured , Crush Injuries/drug therapy , Crush Injuries/metabolism , Ganglia, Spinal/metabolism , HEK293 Cells , Human Umbilical Vein Endothelial Cells , Humans , Ligands , Male , Molecular Docking Simulation , Nerve Regeneration/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Fibroblast Growth Factor/physiology , Sensory Receptor Cells/drug effects , Sensory Receptor Cells/metabolism , Spinal Nerve Roots/injuries , TOR Serine-Threonine Kinases/metabolism
7.
Chimia (Aarau) ; 75(3): 163-168, 2021 Mar 31.
Article in English | MEDLINE | ID: mdl-33766198

ABSTRACT

Metallic nanoparticles of different shape can be used as efficient electrocatalysts for many technologically and environmentally relevant processes, like the electroreduction of CO2. Intense research is thus targeted at finding the morphology of nanosized features that best suits catalytic needs. In order to control the shape and size distribution of the designed nanoobjects, and to prevent their aggregation, synthesis routes often rely on the use of organic capping agents (surfactants). It is known, however, that these agents tend to remain adsorbed on the surface of the synthesized nanoparticles and may significantly impair their catalytic performance, both in terms of overall yield and of product selectivity. It thus became a standard procedure to apply certain methods (e.g. involving UV-ozone or plasma treatments) for the removal of capping agents from the surface of nanoparticles, before they are used as catalysts. Proper design of the operating procedure of the electrocatalysis process may, however, render such cleaning steps unnecessary. In this paper we use poly-vinylpyrrolidone (PVP) capped Ag nanocubes to demonstrate a mere electrochemical, operando activation method. The proposed method is based on an observed hysteresis of the catalytic yield of CO (the desired product of CO2 electroreduction) as a function of the applied potential. When as-synthesized nanocubes were directly used for CO2 electroreduction, the CO yield was rather low at moderate overpotentials. However, following a potential excursion to more negative potentials, most of the (blocking) PVP was irreversibly removed from the catalyst surface, allowing a significantly higher catalytic yield even under less harsh operating conditions. The described hysteresis of the product distribution is shown to be of transient nature, and following operando activation by a single 'break-in' cycle, a truly efficient catalyst was obtained that retained its stability during long hours of operation.

8.
Biotechnol Bioeng ; 118(5): 1962-1972, 2021 05.
Article in English | MEDLINE | ID: mdl-33559890

ABSTRACT

Glycoside hydrolase family 2 (GH2) enzymes are generally composed of three domains: TIM-barrel domain (TIM), immunoglobulin-like ß-sandwich domain (ISD), and sugar-binding domain (SBD). The combination of these three domains yields multiple structural combinations with different properties. Theoretically, the drawbacks of a given GH2 fold may be circumvented by efficiently reassembling the three domains. However, very few successful cases have been reported. In this study, we used six GH2 ß-glucuronidases (GUSs) from bacteria, fungi, or humans as model enzymes and constructed a series of mutants by reassembling the domains from different GUSs. The mutants PGUS-At, GUS-PAA, and GUS-PAP, with reassembled domains from fungal GUSs, showed improved expression levels, activity, and thermostability, respectively. Specifically, compared to the parental enzyme, the mutant PGUS-At displayed 3.8 times higher expression, the mutant GUS-PAA displayed 1.0 time higher catalytic efficiency (kcat /Km ), and the mutant GUS-PAP displayed 7.5 times higher thermostability at 65°C. Furthermore, two-hybrid mutants, GUS-AEA and GUS-PEP, were constructed with the ISD from a bacterial GUS and SBD and TIM domain from fungal GUSs. GUS-AEA and GUS-PEP showed 30.4% and 23.0% higher thermostability than GUS-PAP, respectively. Finally, molecular dynamics simulations were conducted to uncover the molecular reasons for the increased thermostability of the mutant.


Subject(s)
Glucuronidase , Protein Domains/genetics , Protein Engineering/methods , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Fungal Proteins/chemistry , Fungal Proteins/genetics , Fungal Proteins/metabolism , Glucuronidase/chemistry , Glucuronidase/genetics , Glucuronidase/metabolism , Humans , Molecular Dynamics Simulation
9.
Chimia (Aarau) ; 73(11): 922-927, 2019 Nov 01.
Article in English | MEDLINE | ID: mdl-31753073

ABSTRACT

In this work, we discuss the application of a gas diffusion electrode (GDE) setup for benchmarking electrocatalysts for the reductive conversion of CO2 (CO2 RR: CO2 reduction reaction). Applying a silver nanowire (Ag-NW) based catalyst, it is demonstrated that in the GDE setup conditions can be reached, which are relevant for the industrial conversion of CO2 to CO. This reaction is part of the so-called 'Rheticus' process that uses the CO for the subsequent production of butanol and hexanol based on a fermentation approach. In contrast to conventional half-cell measurements using a liquid electrolyte, in the GDE setup CO2 RR current densities comparable to technical cells (>100 mA cm-2) are reached without suffering from mass transport limitations of the CO2 reactant gas. The results are of particular importance for designing CO2 RR catalysts exhibiting high faradaic efficiencies towards CO at technological reaction rates.

10.
Neuroscience ; 404: 510-518, 2019 04 15.
Article in English | MEDLINE | ID: mdl-30731156

ABSTRACT

Brachial plexus root avulsion (BPRA) results in the complete loss of motor function in the upper limb, mainly due to the death of spinal motoneurons (MNs). The survival of spinal MNs is the key to the recovery of motor function. Neuregulin-1 (Nrg1) plays fundamental roles in nervous system development and nerve repair. However, its functional role in BPRA remains unclear. On the basis of our findings that Nrg1 is down-regulated in the ventral horn in a mouse model of BPRA, Nrg1 may be associated with BPRA. Here, we investigated whether recombinant Nrg1ß (rNrg1ß) can enhance the survival of spinal MNs and improve functional recovery in mice following BPRA. In vitro studies on primary cultured mouse MNs showed that rNrg1ß increased the survival rate in a dose-dependent manner, reaching a peak at 5 nM, which increased the survival rate and enhanced the pERK levels in MNs under H2O2-induced oxidative stress. In vivo studies revealed that rNrg1ß improved the functional recovery of elbow flexion, promoted the survival of MNs, enhanced the re-innervation of biceps brachii, and decreased the muscle atrophy. These results suggest that Nrg1 may provide a potential therapeutic strategy for root avulsion.


Subject(s)
Brachial Plexus/drug effects , Motor Neurons/drug effects , Neuregulin-1/therapeutic use , Radiculopathy/drug therapy , Recovery of Function/drug effects , Animals , Brachial Plexus/physiopathology , Cell Survival/drug effects , Cells, Cultured , Male , Mice , Mice, Inbred C57BL , Motor Neurons/physiology , Neuregulin-1/pharmacology , Radiculopathy/physiopathology , Recovery of Function/physiology
11.
Front Chem Sci Eng ; 13(3): 554-562, 2019.
Article in English | MEDLINE | ID: mdl-32215221

ABSTRACT

Glycyrrhetinic acid 3-O-mono-ß-d-glucuronide (GAMG), an important pharmaceutical intermediate and functional sweetener, has broad applications in the food and medical industries. A green and cost-effective method for its preparation is highly desired. Using site-directed mutagenesis, we previously obtained a variant of ß-glucuronidase from Aspergillus oryzae Li-3 (PGUS1), which can specifically transform glycyrrhizin (GL) into GAMG. In this study, a facile method was established to prepare a CaHPO4-PGUS1 hybrid nanoflower for enzyme immobilization, based on protein-inorganic hybrid self-assembly. Under optimal conditions, 1.2 mg of a CaHPO4-PGUS1 hybrid nanoflower precipitate with 71.2% immobilization efficiency, 35.60 mg·g-1 loading capacity, and 118% relative activity was obtained. Confocal laser scanning microscope and scanning electron microscope results showed that the enzyme was encapsulated in the CaHPO4-PGUS1 hybrid nanoflower. Moreover, the thermostability of the CaHPO4-PGUS1 hybrid nanoflower at 55°C was improved, and its half-life increased by 1.3 folds. Additionally, the CaHPO4-PGUS1 hybrid nanoflower was used for the preparation of GAMG through GL hydrolysis, with the conversion rate of 92% in 8 h, and after eight consecutive runs, it had 60% of its original activity.

12.
J Agric Food Chem ; 66(43): 11380-11389, 2018 Oct 31.
Article in English | MEDLINE | ID: mdl-30296070

ABSTRACT

In this study, computation-aided design on the basis of structural analysis was employed to rationally identify a highly dynamic C-terminal region that regulates the stability, expression level, and activity of a GH2 fungal glucuronidase from Aspergillus oryzae Li-3 (PGUS). Then, four mutants with a precisely truncated C-terminal region in different lengths were constructed; among them, mutant D591-604 with a 3.8-fold increase in half-life at 65 °C and a 6.8 kJ/mol increase in Gibbs free energy showed obviously improved kinetic and thermodynamic stability in comparison to PGUS. Mutants D590-604 and D591-604 both showed approximately 2.4-fold increases in the catalytic efficiency kcat/ Km and 1.8-fold increases in the expression level. Additionally, the expression level of PGUS was doubled through a C-terminal region swap with bacterial GUS from E. coli (EGUS). Finally, the robust PGUS mutants D590-604 and D591-604 were applied in the preparation of glycyrrhetinic acid with 4.0- and 4.4-fold increases in concentration through glycyrrhizin hydrolysis by a fed-batch process.


Subject(s)
Aspergillus oryzae/enzymology , Fungal Proteins/metabolism , Glucuronidase/metabolism , Protein Engineering , Biotransformation , Computational Biology , Fungal Proteins/genetics , Glucuronidase/genetics , Glycyrrhetinic Acid/metabolism , Glycyrrhizic Acid/metabolism , Industrial Microbiology , Molecular Dynamics Simulation , Mutant Proteins/metabolism , Protein Structure, Tertiary
13.
Eur J Med Chem ; 157: 50-61, 2018 Sep 05.
Article in English | MEDLINE | ID: mdl-30075402

ABSTRACT

Novel bioactive heterocycles containing a 3,4,5-trimethoxyphenyl fragment as antiproliferative agents by targeting tubulin were synthesized and their preliminary structure activity relationships (SARs) were explored. Among all these chemical agents, 2-(Benzo[d]oxazol-2-ylthio)-N-(4-methoxybenzyl)-N-(3,4,5-trimethoxyphenyl)acetamide (4d) exhibited the potent antiproliferative activity against MGC-803 cells with an IC50 value of 0.45 µM by induction of G2/M pahse arrest and cell apoptosis. In addition, 4d could change the membrane potential (ΔΨ) of the mitochondria against MGC-803 cells. Importantly, 4d acted as a novel tubulin polymerization inhibitor binding to colchicine site with an IC50 value of 3.35 µM.


Subject(s)
Antineoplastic Agents/pharmacology , Heterocyclic Compounds/pharmacology , Microtubules/drug effects , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/chemistry , Humans , Microtubules/metabolism , Models, Molecular , Molecular Structure , Polymerization/drug effects , Structure-Activity Relationship , Tubulin/drug effects , Tubulin/metabolism
14.
J Phys Chem Lett ; 9(16): 4638-4645, 2018 Aug 16.
Article in English | MEDLINE | ID: mdl-30060662

ABSTRACT

N-glycosylation has critical roles in regulating protein stability, but the molecular basis is poorly understood. In this study, we integrated experimental and computational techniques to investigate the mechanism by which full-length N-glycans modulate protein stability from quaternary structure perspective. We found the two inherent N-glycans of ß-glucuronidase expressed in Pichia pastoris function as "glyco-linkers" that hold spatially proximal motifs together to compact the local protein structure. We further designed and placed glyco-linkers in the unusual form of glyco-bridge and glyco-hairpin at the interfaces between domains and monomers with higher structural level, respectively, which conferred dramatically higher kinetic stability and thermodynamic stability than the inherent N-glycans. Our study not only provides unique insight into the interactions between glycans and proteins from a quaternary structure perspective but also facilitates the rational design of N-glycans as general tools that can enhance protein stability.


Subject(s)
Glucuronidase/chemistry , Glycoproteins/chemistry , Polysaccharides/chemistry , Aspergillus oryzae/enzymology , Glucuronidase/genetics , Glycoproteins/genetics , Glycosylation , Molecular Dynamics Simulation , Mutation , Pichia/enzymology , Protein Stability
15.
Front Cell Neurosci ; 11: 381, 2017.
Article in English | MEDLINE | ID: mdl-29238292

ABSTRACT

After complete transection of the thoracic spinal segment, neonatal rats exhibit spontaneous locomotor recovery of hindlimbs, but this recovery is not found in adult rats after similar injury. The potential mechanism related to the difference in recovery of neonatal and adult rats remains unknown. In this study, 342 animals were analyzed. The vascular endothelial growth factor (VEGF) level in spinal segments below injury sites was significantly higher in postnatal day 1 rats (P1) compared with 28-day-old adult rats (P28) following a complete T9 transection. VEGF administration in P28 rats with T9 transection significantly improved the functional recovery; by contrast, treatment with VEGF receptor inhibitors in P1 rats with T9 transection slowed down the spontaneous functional recovery. Results showed more neurons reduced in the lumbar spinal cord and worse local neural network reorganization below injury sites in P28 rats than those in P1 rats. Transynaptic tracing with pseudorabies virus and double immunofluorescence analysis indicated that VEGF treatment in P28 rats alleviated the reduced number of neurons and improved their network reorganization. VEGF inhibition in neonates resulted in high neuronal death rate and deteriorated network reorganization. In in vivo studies, T9 transection induced less increase in the number of microglia in the spinal cord in P1 animals than P28 animals. VEGF treatment reduced the increase in microglial cells in P28 animals. VEGF administration in cultured spinal motoneurons prevented lipopolysaccharide (LPS)-induced neuronal death and facilitated neurite growth. Western blots of the samples of lumbar spinal cord after spinal transection and cultured spinal motoneurons showed a lower level of Erk1/2 phosphorylation after the injury or LPS induction compared with that in the control. The phosphorylation level increased after VEGF treatment. In conclusion, VEGF is a critical mediator involved in functional recovery after spinal transection and can be considered a potential target for clinical therapy.

16.
ACS Appl Mater Interfaces ; 9(44): 39040-39047, 2017 Nov 08.
Article in English | MEDLINE | ID: mdl-29028300

ABSTRACT

Titanium dioxide is widely used in sunscreens because of its strong ultraviolet (UV) light absorbing capabilities and its resistance to discoloration under UV exposure. However, when deposited as a thin film, the high refractive index of titanium dioxide typically results in whiteness and opacity, which limits the use of titanium dioxide for material surfaces, for which long-term natural appearance is of high relevance. Since the whitish appearance is due to the strong light scattering and reflection on the interface of oxide particles and air, one can increase the transparency of TiO2 coatings by forming a continuous TiO2 layer. The purpose of the present article is 2-fold. First, we show that, in the presence of cerium ammonium nitrate, titanium dioxide can be turned from a white powder into a TiO2/Ce xerogel via a facile bottom-up fabrication process. Second, we demonstrate that the transparent TiO2/Ce xerogel can diminish surface deterioration induced by UV light and preserve the natural appearance of the highly abundant biomaterial wood. Furthermore, EPR spectroscopy revealed that the TiO2/Ce xerogel coating suppresses free radical generation on wood surfaces upon UV irradiation. Our research expands the applicability of the protective effect of titanium dioxide to coatings for natural engineering materials, which will become increasingly important in future bioeconomies.

17.
Eur J Med Chem ; 138: 1076-1088, 2017 Sep 29.
Article in English | MEDLINE | ID: mdl-28763643

ABSTRACT

A series of 5,6-diaryl-1,2,4-triazines hybrids bearing a 1,2,3-triazole linker were synthesized by molecular hybridization strategy and evaluated for antiproliferative activity against three selected cancer cell lines (MGC-803, EC-109 and PC-3). The first structure-activity relationship (SAR) for these 5,6-diaryl-1,2,4-triazines is explored in this report with evaluation of 15 variants of the structural class. Among these chemical derivatives, 3-(((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-5,6-diphenyl-1,2,4-triazine (11E) showed the more potent inhibitory effect against three cell lines than 5-Fu. Cellular mechanism studies in MGC-803 cells elucidated 11E inhibited colony formation and arrested cell cycle at G2/M phase. Furthermore, compound 11E caused morphological changes, decreased mitochondrial membrane potential, and induced apoptosis through the apoptosis-related proteins in MGC-803 cells. It was the first time, to our knowledge, that 5,6-diaryl-1,2,4-triazines bearing a 1,2,3-triazole linker were used as potential apoptosis inducers.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Drug Discovery , Triazines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Structure-Activity Relationship , Triazines/chemical synthesis , Triazines/chemistry
18.
Eur J Med Chem ; 127: 87-99, 2017 Feb 15.
Article in English | MEDLINE | ID: mdl-28038329

ABSTRACT

A series of novel formononetin-dithiocarbamate derivatives were designed, synthesized and evaluated for antiproliferative activity against three selected cancer cell line (MGC-803, EC-109, PC-3). The first structure-activity relationship (SAR) for this formononetin-dithiocarbamate scaffold is explored in this report with evaluation of 14 variants of the structural class. Among these analogues, tert-butyl 4-(((3-((3-(4-methoxyphenyl)-4-oxo-4H-chromen-7-yl)oxy)propyl)thio)carbonothioyl)piperazine-1-carboxylate (8i) showed the best inhibitory activity against PC-3 cells (IC50 = 1.97 µM). Cellular mechanism studies elucidated 8i arrests cell cycle at G1 phase and regulates the expression of G1 checkpoint-related proteins in concentration-dependent manners. Furthermore, 8i could inhibit cell growth via MAPK signaling pathway and inhibit migration via Wnt pathway in PC-3 cells.


Subject(s)
Cell Movement/drug effects , Drug Design , Isoflavones/chemistry , Isoflavones/pharmacology , MAP Kinase Signaling System/drug effects , Thiocarbamates/chemistry , Wnt Signaling Pathway/drug effects , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Chemistry Techniques, Synthetic , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Drug Synergism , G1 Phase Cell Cycle Checkpoints/drug effects , Humans , Isoflavones/chemical synthesis , Structure-Activity Relationship
19.
Dalton Trans ; 43(23): 8690-7, 2014 Jun 21.
Article in English | MEDLINE | ID: mdl-24769659

ABSTRACT

From neutral solutions, dimeric 1,3-propanediaminetetraacetato lanthanides (NH4)2[Ln2(1,3-pdta)2(H2O)4]·8H2O [Ln = La, 1; Ce, 2] and K2[Ln2(1,3-pdta)2(H2O)4]·11H2O [Ln = La, 3; Ce, 4] (1,3-H4pdta = 1,3-propanediaminetetraacetic acid, C11H18N2O8) were isolated in high yields. The reaction of excess strontium nitrate with 1 resulted in the formation of a two dimensional coordination polymer [La2(1,3-pdta)2(H2O)4]n·[Sr2(H2O)6]n·[La2(1,3-pdta)2(H2O)2]n·18nH2O (5) at 70 °C. Complexes 1-4 show a similar central molecular structure. The lanthanide ions are coordinated by two nitrogen atoms, four carboxy oxygen atoms from one 1,3-pdta ligand, two from the neighboring 1,3-pdta ligand forming a four-membered ring and two water molecules. Complex 5 has two kinds of dimeric lanthanum unit and extends into a 2D coordination polymer through strontium ions and bridged oxygen atoms, and forms a fourteen membered ring linked by oxygen atoms from carboxy groups of pdta. Complexes 1-4 are soluble in water. The (13)C{(1)H} NMR experiments for complex 1 were tested in solution. Thermal products from 1 and 5 show good catalytic activities towards the oxidative coupling reaction of methane (OCM). The conversion of methane and selectivity to C2 reached 29.7% and 51.7% at 750 °C for the product of 5. From TGA, XRD and SEM analyses, the thermal products from 1 and 5 are rod- and poly-shaped, which are assigned as lanthanum oxocarbonate and a mixture of La2O3, SrCO3 and La2O2CO3 for 1 and 5, respectively. The precursor method is favorable for the formation of regular shaped mixed oxides.

20.
Exp Parasitol ; 115(3): 242-6, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17069805

ABSTRACT

The nematode Haemonchus contortus (H. contortus) is one of the most pathogenic and economically important parasites of sheep. A 24 kDa protein is one of the important components in H. contortus excretory/secretory (ES), which was shown to have important biological function. In our research, the cDNA of its open reading frame (ES24) was obtained and analyzed. Then the ES24 was sub-cloned into pET-30a expression vector. The recombinant vector that codes hexahistidyl peptide fusion protein (His-ES24) was transformed into Escherichia coli BL21 (DE3) strain. After induction, a high expression level of His-ES24 was found at 6h taking about 26% of the total bacterial protein analyzed by gel thin-layer scanning. The expressed His-ES24 was purified and then used in an enzyme-linked immunosorbent assay (ELISA) to detect specific antibodies in serum samples. The ELISA was able to differentiate between H. contortus-infected sheep serum and Fasciola hepatica-infected sheep serum or non-infected sheep serum. No cross-reaction was observed in sheep sera that have been experimentally infected with F. hepatica. A total of 153 field sheep serum samples conserved in our laboratory were examined using the His-ES24 ELISA, and 82 (53.6%) of them were found seropositive to H. contortus. Our results demonstrate that the prokaryotic-expressed His-ES24 might be a useful diagnostic reagent for epidemiological studies of H. contortus in sheep.


Subject(s)
Enzyme-Linked Immunosorbent Assay/methods , Haemonchiasis/veterinary , Haemonchus/isolation & purification , Helminth Proteins , Sheep Diseases/diagnosis , Animals , Antibodies, Helminth/blood , Antigens, Helminth/genetics , Antigens, Helminth/immunology , Antigens, Helminth/isolation & purification , Cloning, Molecular , Enzyme-Linked Immunosorbent Assay/standards , Haemonchiasis/diagnosis , Haemonchus/chemistry , Haemonchus/genetics , Haemonchus/immunology , Helminth Proteins/genetics , Helminth Proteins/immunology , Helminth Proteins/isolation & purification , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Recombinant Proteins/isolation & purification , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Sheep
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