Alfalfa (Medicago sativa) is a highly valuable perennial forage legume that suffers from autotoxicity, which decreases plant resistance, reduces soil fertility, causes serious soil-borne diseases, ...and promotes ecological imbalance. We evaluated the effects of autotoxicity on the seed germination of 22 alfalfa varieties, and then elucidated the oxidative damage and lipid peroxidation in two alfalfa varieties with contrasting autotoxicity tolerances. The technique for order of preference by similarity to ideal solution (TOPSIS) method was used to rank the germination of the 22 alfalfa varieties when exposed to six autotoxic concentrations (0, 0.025, 0.075, 0.125, 0.175, and 0.225 g∙mL−1). We found WL656HQ and 3105C to be autotoxicity-tolerant and autotoxicity-sensitive varieties, respectively. The germination index mainly affects the comprehensive allelopathic index of WL656HQ and 3105C, which were the simple vigor index and radicle length according to the random forest model, respectively. 3105C eliminates reactive oxygen species (ROS) via antioxidant enzymes and antioxidants under T1 (0.025 g∙mL−1), but the oxidative stress system and the oxidative scavenging system cannot maintain the balance under T2 (0.125 g∙mL−1), causing oxidative bursts. In comparison, WL656HQ used its oxidative scavenging system (peroxidase (POD), ascorbate peroxidase (APX), and glutathione reductase (GR)) to maintain its redox dynamic balance by removing excess ROS at all concentrations. In conclusion, the positive and negative indicators of autotoxicity for the two varieties were ascorbate (ASA) and hydroxyl free radicals (OH•), and proline (Pro) and dehydroascrobate (DHA), respectively. The most sensitive autotoxic concentrations of 3105C and WL656HQ were T2 (0.125 g∙mL−1) and T1 (0.025 g∙mL−1), respectively.
Huagaimu (
Manglietiastrum sinicum
) trees are critically endangered species and classified as a plant species with extremely small populations in China. Rhizospheres and bulk soils prokaryotic ...communities play an important role to protect and promote plants health and growth. However, the compositions and structures of prokaryotic communities in wild and reintroduced
M. sinicum
rhizospheres and bulk soils are still poorly understood. In the present study, prokaryotic communities in wild and reintroduced
M. sinicum
rhizospheres and bulk soils were compared using high-throughput sequencing. Thirty-two phyla, 76 classes, 193 orders, 296 families, and 470 genera of prokaryotes were obtained. Proteobacteria and Acidobacteria were the two most abundant phyla in all soil samples. The compositions and structures of prokaryotic communities were overall similar, and the abundance of some taxa varied significantly among soil samples. Soil prokaryotic communities were significantly affected by soil pH, total nitrogen, total phosphorus, and total potassium. Eleven of predicted functions were significantly different among the four soil groups. This study provides for the first insights into the compositions, structures, and potential functions of prokaryotic communities associated with wild and reintroduced
M. sinicum
rhizospheres and bulk soils, and providing a foundation for future research to help protect this endangered species.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
An innovative approach to improve the quality of TiC-Ti5Si3 composite coating was demonstrated. TiC-Ti5Si3 composite coatings had been successfully prepared by in-situ synthesis. However, there were ...still problems with a low degree of reaction and poor quality of the resulting coating. In the present investigation Ti-SiC composite powders and heat-treated Ti-SiC composite powders were plasma sprayed onto the TC4 titanium alloy, respectively, for preparing titanium carbide‑titanium silicide composite coatings. The results show that the phases composition of the two composite coatings obtained by plasma spraying Ti-SiC composite powders and heat-treated Ti-SiC composite powders were TiC, Ti5Si3 and SiC. However, the coating obtained by plasma spraying heat-treated Ti-SiC composite powders had higher density and more uniform distribution, and the microhardness value of the coating was increased by 34.3%, and the wear rate was reduced by 48.6% compared with the coating obtained by plasma spraying Ti-SiC composite powders.
Schematic illustration of phase transformation of Ti-SiC composite powder during heat treatment at 1200 °C for 1 h (Ar gas protection). Display omitted
•TiC, Ti5Si3 and Ti3SiC2 were formed in Ti-SiC composite powder after heat treatment.•The coating obtained by heat treated Ti-SiC powder had better density and structure.•Heat treatment of Ti-SiC powder could improve the properties of the Ti-SiC coating.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Due to the complicated pathogenesis of Alzheimer's disease (AD), the development of multitargeted agents to simultaneously interfere with multiple pathological processes of AD is a potential choice. ...Glycogen synthase kinase-3β (GSK-3β) plays a vital role in the AD pathological process. In this study, we discovered a novel 1
-pyrrolo2,3-bpyridine derivative B10 as a GSK-3β inhibitor that features with a quinolin-8-ol moiety to target the metal dyshomeostasis of AD. B10 potently inhibited GSK-3β with an IC
of 66 ± 2.5 nM. At the concentration of 20 μM, B10 increased β-catenin abundance (β-catenin/GAPDH: 0.83 ± 0.086 vs. 0.30 ± 0.016), phosphorylated GSK-3β at Ser9 (p-GSK-3β/GAPDH: 0.53 ± 0.045 vs. 0.35 ± 0.012), and decreased the phosphorylated tau level (p-tau/GAPDH: 0.33 ± 0.065 vs. 0.83 ± 0.061) in SH-SY5Y cells. Unlike other GSK-3β inhibitors, B10 had a direct effect on Aβ by inhibiting Aβ
aggregation and promoting the Aβ
aggregate disassociation. It selectively chelated with Cu
, Zn
, Fe
and Al
, and targeted AD metal dyshomeostasis. Moreover, B10 effectively increased the mRNA expression of the recognized neurogenesis markers, GAP43, N-myc, and MAP-2, and promoted the differentiated neuronal neurite outgrowth, possibly through the GSK-3β and β-catenin signal pathways. Therefore, B10 is a potent and unique GSK-3β inhibitor that has a direct on Aβ and serves as a multifunctional anti-AD agent for further investigations.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Acoustic array bunching is an effective method to realize the directional radiation of underwater plasma sound source (UPSS). The prebreakdown time is one of the decisive factors for the performance ...of acoustic array bunching. The working characteristics of the underwater plasma sound source and the prebreakdown process of underwater plasma arc discharge are deeply analyzed. The precondition of plasma sound source array bunching is given by analyzing the waveforms of electrical signals and acoustic signals. Through the experiments of arc discharge based on different aqueous solutions, a feasible scheme of underwater plasma sound source array bunching in salt water is proposed. Through the arc discharge experiments based on different system discharge parameters, the variation of prebreakdown time under the influence of different charging voltage, conductivity, and other parameters was studied. The experimental results show that the prebreakdown time decreases with the increase of charging voltage and conductivity. At the same time, the discharge current increases, the oscillation time decreases, and the energy injection rate on the electrode accelerates. The research results are helpful to understand the prebreakdown mechanism of plasma sound source and optimize the underwater plasma sound source array bunching scheme and the acoustic shock wave waveform.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective
Macitentan is a new choice for pulmonary hypertension treatment which is converted to active metabolite ACT132577 by human cytochrome P450 3A4. Human cytochrome P450 3A4 often occurred gene ...mutations. Gene polymorphism might cause a variety of changes of protein expression and thus give rise to metabolic difference. The aim of this study was to investigate the catalytic characteristics of 27 CYP3A4 protein variants on the metabolism of macitentan in vitro.
Method
The incubation mixtures (final volume of 200 μl in 1 m PBS) consisted of 1 pmol wild‐type CYP3A4.1 or other CYP3A4 protein variants, 2.38 pmol CYP b5 and macitentan (10–600 μm) with 1 mm NADPH. All specimens were processed using same approach with acetonitrile precipitation. The metabolite of macitentan was analysed by ultra performance liquid chromatography–tandem mass spectrometry.
Key finding
Most CYP3A4 protein variants (CYP3A4.9, .11, .12, .13, .17, .20, .23, .24, .28, .29, .33, .34) exhibited a sharp decrease, meanwhile nearly one in five variants (CYP3A4.3, .4, .5, .10, .15, .16) showed a significant rise in intrinsic clearance. The relative clearance of CYP3A4 protein variants was ranged from 5.53 to 501.00%.
Conclusion
Twenty‐seven CYP3A4 protein variants displayed different catalytic characteristics towards macitentan in vitro, especially CYP3A4.5, .17, .20, .23. It is important to pay more attention to the dosage of macitentan in order to get better treatment for pulmonary arterial hypertension.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The effect of total organic carbon (TOC) on the prokaryotic community structure in situ has been rarely known. This study aimed to determine the effect of TOC level on the composition and networks of ...archaeal and bacterial communities in the sediments of Dianchi Lake, one of the most eutrophic lakes in China. Microbial assemblages showed significantly associations with TOC. Moreover, relatively high and low TOC formed taxonomic differences in prokaryotic assemblages. According to the results, the most abundant bacteria across all samples were identified as members of the phyla Proteobacteria, Nitrospirae, Chloroflexi, Firmicutes and Ignavibacteriae. The dominant groups of archaea consisted of Euryarchaeota, Woesearchaeota DHVEG-6, Bathyarchaeota and WSA2. Lastly, the meta-analysis results highlighted that the low TOC (LT) prokaryotic community structure is larger and more complex compared to moderate TOC (MT). On the whole, the prokaryotic community structure is obviously distinct among groups with different TOC levels, and LT communities may interact with each other strongly in the Dianchi Lake sediment. This study can provide more insights into prokaryotic assemblages in eutrophic lake sediment and provide suggestions for the restoration and maintenance of sediment ecosystems.
Fructus Alpiniae oxyphyllae (A. oxyphylla) is a traditional herb which is widely used in East Asian for the treatment of dyspepsia, diarrhea, abdominal pain, poor memory, inflammatory conditions and ...cancer.
The cytotoxic activities of ethanol extract (EE) and five extract layers including petroleum ether (PE), dichloromethane (DCLM), acetoacetate (EtOAc), n-Butanol (n-Bu) and water fractions (WF) of A. oxyphylla were tested on HepG2, SW480, MCF-7, K562 and HUVEC cell lines using MTT assay and LDH release assay. The component analysis was performed on HPLC with gradient elution. Hoechst 33342 staining, DCFH-DA fluorescence microscopy, flow cytometry analysis, western blot and migration assays were carried out to determine the anti-cancer mechanisms of PE.
MTT analysis showed that EE, PE and DCLM could inhibit cell proliferation on HepG2, SW480, MCF-7, K562 and HUVEC cell lines, especially PE fraction. HPLC analysis pointed out five main components which may contribute to the anti-proliferative activity of PE. Further study showed that PE increased LDH release, induced apoptosis, disrupted mitochondrial membrane potential and elevated intracellular reactive oxygen species (ROS) in HepG2 cells, whereas the antioxidant N-acetyl-l-cysteine (NAC) prevented PE-induced ROS generation. The results of western blot revealed that PE induced apoptosis in HepG2 cells by enhancing Bax/Bcl-2 ratio, increasing cytochrome c in cytosol and activating caspase-3/9. Meanwhile, high levels of ROS could induce DNA damage-mediated protein expression, AKT, ERK inactivation and SAPKs activation. Furthermore, PE conspicuously blocked the migration of HUVEC cells.
The present results demonstrated that PE induced apoptosis in HepG2 cells may be via a ROS-mediated signaling pathway.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Neuropathic pain is a common neurobiological disease involving multifaceted maladaptations ranging from gene modulation to synaptic dysfunction, but the interactions between synaptic dysfunction and ...the genes that are involved in persistent pain remain elusive. In the present study, we found that neuropathic pain induced by the chemotherapeutic drug paclitaxel or L5 ventral root transection significantly impaired the function of GABAergic synapses of spinal dorsal horn neurons via the reduction of the GAD67 expression. We also found that mir-500 expression was significantly increased and involved in the modulation of GAD67 expression via targeting the specific site of Gad1 gene in the dorsal horn. In addition, knock-out of mir-500 or using mir-500 antagomir rescued the GABAergic synapses in the spinal dorsal horn neurons and attenuated the sensitized pain behavior in the rats with neuropathic pain. To our knowledge, this is the first study to investigate the function significance and the underlying molecular mechanisms of mir-500 in the process of neuropathic pain, which sheds light on the development of novel therapeutic options for neuropathic pain.
Neuropathic pain is a common neurobiological disease involving multifaceted maladaptations ranging from gene modulation to synaptic dysfunction, but the underlying molecular mechanisms remain elusive. The present study illustrates for the first time a mir-500-mediated mechanism underlying spinal GABAergic dysfunction and sensitized pain behavior in neuropathic pain induced by the chemotherapeutic drug paclitaxel or L5 ventral root transection, which sheds light on the development of novel therapeutic options for neuropathic pain.
A new phloroglucinol derivative, named eucalyptin B (1), along with five related known compounds (2 – 6), was isolated from the fruits of Eucalyptus globulus. Their structures were elucidated by ...means of 1D‐ and 2D‐NMR spectroscopy, with the absolute configuration of 1 determined by electronic circular dichroism (ECD) calculations. All isolated compounds (1 – 6) were evaluated for their cytotoxic activities against lung (A549), breast (4T1), and skin (B16F10) cancer cell lines. On the basis of cell viability assay, the cytotoxic activity of eucalyptin B (1) was further confirmed by apoptosis assay. Additionally, after treatment with eucalyptin B (1), the apoptosis factor proteins (Bcl2 and Bax) and caspase‐3 levels in A549 cells were also determined by Western‐blot analysis. By cytotoxic assay, eucalyptin B (1) exhibited potent cytotoxicity against A549 cells with an IC50 value of 1.51 μm and induced concentration dependent apoptosis of up to 49%. Additionally, eucalyptin B (1) inhibited 5‐fold and increased 10‐folds in the level of Bcl2 and Bax, respectively. Furthermore, the 11‐fold increase in the level of caspase‐3 confirmed eucalyptin B (1) activated caspase dependent apoptosis pathway. In conclusion, the isolated compound eucalyptin B (1) has promising cytotoxic activity in tumor cells, especially in A549.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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