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1.
Biomed Pharmacother ; 125: 109922, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32007919

RESUMO

Quercetin is a natural product that has been shown to induce tumor apoptosis and necrosis through multiple mechanisms. Tumor-induced myeloid-derived suppressor cell (MDSC) expansion negatively regulates the immune response by inhibiting T cell function through signal transducer and activator of transcription 3 (STAT3) activation, thereby facilitating tumor escape from host immune surveillance. Thus MDSC is an attractive target for cancer immunotherapy to enhance cytotoxic T cell responses. However, the effects of quercetin on MDSC are poorly understood. Here, we demonstrate that quercetin treatment enhanced mouse- and human- derived granulocytic-myeloid-derived suppressor cells (G-MDSC) survival and promoted the secretion of T cell-suppressive factors in vitro. Bioinformatics analysis further showed that quercetin was highly correlated with the estrogen receptor signaling pathway, which was confirmed by quantitative reverse transcription-polymerase chain reaction and flow cytometric analysis. These findings highlight the potential advantages and feasibility of quercetin in reinforcing the suppressive property of G-MDSC. Thus impact of G-MDSC should be taken into consideration when quercetin is applied to tumor therapy.

2.
Nat Cell Biol ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066906

RESUMO

Clustered regularly interspaced short palindromic repeats (CRISPR), CRISPR interference and programmable base editing have transformed the manipulation of eukaryotic genomes for potential therapeutic applications1-4. Here, we exploited CRISPR interference and programmable base editing to determine their potential in editing a TERT gene promoter-activating mutation, which occurs in many diverse cancer types, particularly glioblastoma5-8. Correction of the -124C>T TERT promoter mutation to -124C was achieved using a single guide RNA (sgRNA)-guided and catalytically impaired Campylobacter jejuni CRISPR-associated protein 9-fused adenine base editor (CjABE). This modification blocked the binding of members of the E26 transcription factor family to the TERT promoter, reduced TERT transcription and TERT protein expression, and induced cancer-cell senescence and proliferative arrest. Local injection of adeno-associated viruses expressing sgRNA-guided CjABE inhibited the growth of gliomas harbouring TERT-promoter mutations. These preclinical proof-of-concept studies establish the feasibility of gene editing as a therapeutic approach for cancer and validate activated TERT-promoter mutations as a cancer-specific therapeutic target.

3.
Int J Mol Sci ; 21(3)2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32041257

RESUMO

In the model species Arabidopsis thaliana, FRIGIDA (FRI) is a key regulator of flowering time and can inhibit flowering without vernalization. However, little information is available on the function in the Rosaceae family. Loquat (Eriobotrya japonica) belongs to the family Rosaceae and is a distinctive species, in which flowering can be induced without vernalization, followed by blooming in late-autumn or winter. To investigate the functional roles of FRI orthologs in this non-vernalization species, we isolated an FRI ortholog, dubbed as EjFRI, from loquat. Analyses of the phylogenetic tree and protein sequence alignment showed that EjFRI is assigned to eurosids I FRI lineage. Expression analysis revealed that the highest expression level of EjFRI was after flower initiation. Meanwhile, EjFRI was widely expressed in different tissues. Subcellular localization of EjFRI was only detected to be in the nucleus. Ectopic expression of EjFRI in wild-type Arabidopsis delayed flowering time. The expression levels of EjFRI in transgenic wild-type Arabidopsis were significantly higher than those of nontransgenic wild-type lines. However, the expression levels of AtFRI showed no significant difference between transgenic and nontransgenic wild-type lines. Furthermore, the upregulated AtFLC expression in the transgenic lines indicated that EjFRI functioned similarly to the AtFRI of the model plant Arabidopsis. Our study provides a foundation to further explore the characterization of EjFRI, and also contributes to illuminating the molecular mechanism about flowering in loquat.

4.
Acta Physiol (Oxf) ; : e13439, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900976

RESUMO

AIM: To explore the role of the histidine triad nucleotide-binding 2 (HINT2) protein in heart failure. METHODS: Neonatal mouse ventricle myocytes (NMVMs) and myocardial infarction-induced heart failure mice were used for in vitro or in vivo experiments. Adenovirus (ADV) and adeno-associated virus serum type 9 (AAV9) vectors were used to regulate HINT2 expression. The expression of HINT2 was determined by quantifying the mRNA and protein levels. Cell survival was analysed using the CCK-8 kit and TUNEL staining. Mitochondrial function was determined by the mitochondrial membrane potential and oxygen consumption rates. AAV9-HINT2 was injected 24 h post-myocardial infarction following which transthoracic echocardiography and histological analyses were performed after 4 weeks. Positron emission tomography tomography-computed tomography (PET/CT) and targeted metabolomics analyses were used to explore the metabolic status in vivo. NAD levels were measured using a colorimetric kit. Computer-simulated rigid body molecular docking was performed using AUTODOCK4. Molecule binding kinetics assays were performed using biolayer interferometry. RESULTS: HINT2 was down-regulated in NMVMs in hypoxia. ADV-HINT2-induced HINT2 overexpression improved NMVM survival after exposure to hypoxia. Mitochondrial function was preserved in the ADV-HINT2 group under hypoxic conditions. In vivo experiments showed that cardiac function and metabolic status was preserved by HINT2 overexpression. HINT2 overexpression restored mitochondrial NAD levels; this was dependent on nicotinamide mononucleotide (NMN). Using computer-simulated molecular docking analysis and biolayer interferometry, we observed that HINT2 potentially binds and associates with NMN. CONCLUSION: HINT2 overexpression protects cardiac function in adult mice after myocardial infarction by maintaining mitochondrial NAD homeostasis.

5.
Nat Chem ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907403

RESUMO

Force can induce remarkable non-destructive transformations along a polymer, but we have a limited understanding of the energy transduction and product distribution in tandem mechanochemical reactions. Ladderanes consist of multiple fused cyclobutane rings and have recently been used as monomeric motifs to develop polymers that drastically change their properties in response to force. Here we show that [4]-ladderane always exhibits 'all-or-none' cascade mechanoactivations and the same stereochemical distribution of the generated dienes under various conditions and within different polymer backbones. Transition state theory fails to capture the reaction kinetics and explain the observed stereochemical distributions. Ab initio steered molecular dynamics reveals unique non-equilibrium dynamic effects: energy transduction from the first cycloreversion substantially accelerates the second cycloreversion, and bifurcation on the force-modified potential energy surface leads to the product distributions. Our findings illustrate the rich chemistry in closely coupled multi-mechanophores and an exciting potential for effective energy transduction in tandem mechanochemical reactions.

6.
Sci Total Environ ; 711: 135120, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31822413

RESUMO

Excess natural organic matter (NOM) in water not only lead to unpleasant black color and dissolved oxygen depletion in wastewater and natural water body but also causes carcinogenic chlorinated organic byproduct during drinking water chlorine disinfection. We try to develop a novel cost-effective and green technology for water NOM removal. In our simulated NOM removal process using humic acid (HA) as typical organic matter, we find that mesoporous nano-MgO performs an abnormally high NOM removal capacity (1260 mg-HA/g-MgO, or 446 mgC/g-MgO) when coupled with microfiltration membrane separation, which can't be illustrated by traditional adsorption mechanism. Actually, Mg2+ from dissolved Mg(OH)2 contributes ∼ 92% NOM removal via coagulation while Mg(OH)2 is responsible for the residue ∼ 8% via adsorption. MgO serves as a two-in-one coagulant and adsorbent. The MgO treatment process is highly pH sensitive and weak acidic condition is favored for high NOM removal efficiency. MgO can be regenerated for more than 10 circulations by annealing Mg(OH)2/Mg-NOM composite at 500 °C, so that our MgO recycling process will be sustainable without the need of continuous chemical purchase. More importantly, no solid waste is generated in this novel process. This MgO-recycling NOM-removal process is simple, efficient, and sustainable for water NOM removal and will be significant in promoting novel sustainable technologies for NOM- or HA-related water remediation and treatment while minimizing the generation of solid waste.

7.
Mol Med Rep ; 21(2): 607-614, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31789412

RESUMO

Ventilator­induced lung injury (VILI) is a life­threatening condition caused by the inappropriate use of mechanical ventilation (MV). However, the precise molecular mechanism inducing the development of VILI remains to be elucidated. In the present study, it was revealed that the calcineurin/NFATc4 signaling pathway mediates the expression of adhesion molecules and proinflammatory cytokines essential for the development of VILI. The present results revealed that a high tidal volume ventilation (HV) caused lung inflammation and edema in the alveolar walls and the infiltration of inflammatory cells. The calcineurin activity and protein expression in the lungs were increased in animals with VILI, and NFATc4 translocated into the nucleus following calcineurin activation. Furthermore, the translocation of NFATc4 and lung injury were prevented by a calcineurin inhibitor (CsA). Thus, the present results highlighted the critical role of the calcineurin/NFATc4 signaling pathway in VILI and suggest that this pathway coincides with the release of ICAM­1, VCAM­1, TNF­α and IL­1ß.

8.
Sci Total Environ ; 704: 135410, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31791757

RESUMO

The proper disposal of copper (Cu) polluted plant residues after phytoremediation has attracted extensive attention. In this study, the Cu-polluted biogas residue produced through anaerobic digestion was applied directly. Wheat, soybean and pakchoi were grown in pots for four seasons over two years. The application dosage of Cu-polluted biogas residue was evaluated by measuring growth conditions of crops, Cu content in edible parts, and amelioration of saline-alkali soil. The results showed that the biomass of the crops, the content of soil organic matter, total N and available P and microbial diversity can be improved, and the Cu concentration of the edible parts was all lower than limit standard. Amendment with 2% biogas residue enhanced the growth of beneficial bacteria and fungi, and decreased the relative abundances of potentially pathogenic fungi in the saline-alkali soil. The results of this study provide a basis for the safe utilisation of copper-polluted plant residues.

9.
Mol Immunol ; 117: 168-179, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31812793

RESUMO

OBJECTIVE: This investigation was intended to elucidate lncRNA-miRNA networks that could explain inflammation underlying sepsis progression. METHODS: In the first place, four kinds of mice models were established, namely, SHAM group (n = 30), trauma (TH) group (n = 30), lipopolysaccharide (LPS) group (n = 30) and TH + LPS group (n = 30). Their lung, spleen and liver tissues were gathered for determination of TNF-α, IL-6, IL-10 and MCP-1 levels. Furthermore, mouse mononuclear macrophage leukemia cell line (RAW264.7) was stimulated by LPS to establish inflammation cell models. Then si-NEAT1s, pcDNA3.1-NEAT1, miR-495-3p mimic, miR-495-3p inhibitor, miR-NC, miR-211 mimic and miR-211 inhibitor were, respectively, transfected into the cells, so as to observe the impacts of NEAT1, miR-495-3p and miR-211 on cytokine levels released by the cells. RESULTS: The survival condition of mice in the TH + LPS group was undesirable, in relative to mice in the LPS group and SHAM group (both P < 0.05). High-level NEAT1 and low-level miR-495-3p/miR-211 were associated with poor survival of mice in the TH+LPS group (P < 0.05). Additionally, the correlation between NEAT1/miR-495-3p/miR-211 level and cytokine level was the strongest among TH+LPS-treated mice, in comparison to mice treated by TH or LPS. Furthermore, up-regulation of NEAT1 level and down-regulation of miR-495-3p/miR-211 level could aggravate inflammation in LPS-treated RAW264.7 cells. The miR-495-3p and miR-211 herein, were both subjected to sponging of NEAT1, possibly affected inflammation responses in RAW264.7 cells, respectively, through modulating STAT3 and PI3K/AKT signaling. CONCLUSION: LncRNA NEAT1 exhibited great potential sepsis diagnosis and treatment, considering its modifying miR-495-3p/STAT3 axis and miR-211/PI3K/AKT axis in inflammation cell models.

10.
J Cell Biochem ; 121(2): 1747-1758, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31633225

RESUMO

miR-19a has been shown to be involved in coronary microvascular obstruction injury; however, the underlying molecular mechanisms remain unknown. In our study, we tried to explore the role of miR-19a in cardiomyocyte apoptosis and calcium overload in vivo and in vitro induced by hypoxia. We established the acute myocardial infarction (AMI) rat model by ligating the left anterior descending artery. The expression of miR-19a in the infarct zone of AMI rats and myocardial tissue in the same position in sham rats was analyzed using RT-qPCR while Na(+) /H(+) exchanger 1 (NHE-1) was detected by Western blotting. We also observed the effects of overexpressing miR-19a or administering an NHE-1 inhibitor (cariporide) on hypoxia-induced (HI) calcium overload and apoptosis in primary cardiomyocytes. In addition, dual-luciferase reporter assays were conducted to investigate the potential target of miR-19a on NHE-1. Decreased miR-19a expression, as well as increased apoptosis and NHE-1 expression, were observed in the AMI model. Furthermore, after hypoxia stimulation, miR-19a was gradually reduced as time increased in primary cardiomyocytes. Overexpressing miR-19a using mimics ameliorated the increase in NHE-1 in hypoxic cardiomyocytes and thereby reduced the HI cell calcium overload and cell apoptosis rate from 12.32% to 9.5% (P < .01). In addition, the dual-luciferase reporter gene assay results verified that NHE-1 was the direct target of miR-19a. Our findings suggest that miR-19a activation can attenuate HI cardiomyocyte apoptosis by downregulating NHE-1 expression and decreasing calcium overload.

11.
J Am Chem Soc ; 142(3): 1186-1189, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31880922

RESUMO

Enol ethers are widely used as quenching reagents for Grubbs catalysts. However, we report the surprisingly effective ring-opening metathesis polymerization (ROMP) of cyclic enol ethers, because the resulting electron-rich ruthenium alkylidene complex remains active toward metathesis of electron-rich olefins, despite its deactivation toward hydrocarbon olefins. We demonstrate the first example of ROMP of cyclic enol ethers, using 2,3-dihydrofuran as the monomer, producing a new type of degradable and depolymerizable poly(enol ether). The polymers exhibited perfect regioregularity, and their molecular weights can be regulated by the loading of Grubbs initiators or by the use of a linear vinyl ether as the chain transfer agent. We also developed protocols to deactivate the catalyst following metathesis of enol ethers and cleave the catalyst off the resulting polymers using H2O2 oxidation. The resulting poly(dihydrofuran) can be recycled to monomer via depolymerization with Grubbs catalyst or degraded to small molecules by hydrolysis under acidic conditions. This work opens exciting opportunities for a new class of ROMP monomers that lead to degradable polymers.

12.
Ecotoxicol Environ Saf ; 190: 110105, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31884325

RESUMO

Copper (Cu) toxicity has a deleterious effect on plant growth, and different nitrogen (N) forms have significantly different impacts on the uptake and accumulation of heavy metals by plants. However, it remains unclear how excess Cu inhibits the growth of rice seedlings under different N forms. Here, we examined the mechanism of Cu toxicity inhibiting the growth of rice supplied with different N forms. Rice seedlings were grown in a nutrient solution with 0.81 mmol L-1 N, as ammonium (NH4+), nitrate (NO3-) and NH4+ + NO3-, or without N (0 N) in the presence of 0.2 µmol L-1 CuSO4 or 10 µmol L-1 CuSO4. The inhibition of shoot growth under excess Cu was more pronounced in plants that were supplied with NO3- than NH4+; such inhibition was not induced by higher Cu concentration in shoots. Applied with NO3- alone increased solution pH value up to 6.2, but supplied with NH4+ alone and NH4+ + NO3- decreased solution pH value to 4.0 and 4.2, respectively. The increment of solution pH reduced Cu concentration in shoots of rice supplied with NO3- alone. Copper toxicity decreased NO3- concentrations in rice seedlings that were supplied with NO3- alone but increased the NH4+ concentrations in plants that were supplied with NH4+ or NH4+ + NO3-. High Cu levels reduced the uptake of NO3- in roots by the analysis of net NO3- flux and NO3- assimilation enzymes activity. Under excess Cu, the transcript levels of OsNPF6.5, OsNPF2.2 and OsNPF2.4 genes were suppressed, while OsNRT2.1, OsNRT2.2 and OsNAR2.1 were raised in roots. In conclusion, Cu toxicity inhibits NO3- uptake and upward translocation by modulating the expression level of NO3- transporter genes. The reduction in the concentrations of NO3- and total N decreased shoot growth of rice seedlings when N was supplied as NO3-. Hence, rice seedlings supplied with NO3- had lower shoot biomass than those with NH4+ under Cu stress.

13.
Sci Total Environ ; 699: 134342, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31678885

RESUMO

Heterogeneous photodegradation is limited at high catalyst concentrations because of the scattering and reflection of the particulate catalysts. To further improve the efficiency of photodegradation and the use of space in photoreactors at high catalyst concentrations, Ga3+ was doped into Zn2SiO4 to introduce positively charged traps to capture photo-generated electrons and, thus, achieve long lifetime charge separation. In this strategy, Zn2SiO4:Ga3+ was obtained as a two-in-one (persistent luminescence and catalysis) persistent photocatalyst for the efficient photodegradation of a household insecticide, permethrin. Zn2SiO4:Ga3+ possesses an UV afterglow property. Zn2SiO4:Ga3+ can store UV irradiation energy as long lifetime separated electron/hole pairs at the solution surface and then deliver this energy deep into the bulk of the solution, thus taking full advantage of the photoreactor. High catalyst concentrations are preferred for improving the persistent photodegradation efficiency. The UV persistent photocatalytic strategy and the persistent Zn2SiO4:Ga3+ catalyst are significant for designing fast photocatalytic reactors with high catalyst concentrations.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31797570

RESUMO

The objectives of the present study were to evaluate the bioequivalence of 2 tablet formulations of prucalopride, generic and branded, and to investigate relevant pharmacokinetic and safety profiles. This study was designed as a randomized, open-label, fasting, single-dose, crossover, and dual-period trial. After overnight fasting, 12 subjects were given prucalopride tablets via oral administration, and blood specimens were obtained up to 96 hours after dosing. Prucalopride concentrations in plasma were measured using ultraprecision liquid chromatography-tandem mass spectrometry followed by calculation of pharmacokinetic parameters. The safety of prucalopride was assessed throughout the study. The pharmacokinetics of prucalopride can be defined as a 2-compartment model with a long elimination phase. No significant differences were observed between the pharmacokinetic profiles of the generic and branded prucalopride tablets. Bioequivalence was evaluated using 90%CIs for the ratio test/reference of log area under the concentration-time curve over 96 hours, log area under the concentration-time curve to infinity, and log peak concentration from generic and branded tablets, which were 100.06-109.94%, 100.63-110.32%, and 95.84-113.08%, respectively. During administration of the medication, there were 18 adverse events in 6 subjects in the test formulation group and 19 cases of adverse events in 6 subjects in the reference formulation group (P > .05). No severe adverse effects were detected. These results suggest that generic and branded prucalopride tablets are bioequivalent and show similar safety profiles.

15.
Genomics Proteomics Bioinformatics ; 17(4): 402-414, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31811942

RESUMO

Neuropsychiatric disorders affect hundreds of millions of patients and families worldwide. To decode the molecular framework of these diseases, many studies use human postmortem brain samples. These studies reveal brain-specific genetic and epigenetic patterns via high-throughput sequencing technologies. Identifying best practices for the collection of postmortem brain samples, analyzing such large amounts of sequencing data, and interpreting these results are critical to advance neuropsychiatry. We provide an overview of human brain banks worldwide, including progress in China, highlighting some well-known projects using human postmortem brain samples to understand molecular regulation in both normal brains and those with neuropsychiatric disorders. Finally, we discuss future research strategies, as well as state-of-the-art statistical and experimental methods that are drawn upon brain bank resources to improve our understanding of the agents of neuropsychiatric disorders.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31831173

RESUMO

APETALA3: (AP3) encodes a floral homeotic class B-function MADS-box protein and plays crucial roles in petal and stamen development. To better understand the functional roles of AP3 orthologs in Eriobotrya, we isolated and identified an AP3 ortholog, referred to as EjAP3, from Eriobotrya japonica. Analyses of protein sequence and phylogenetic tree showed that the EjAP3 was assigned to the rosids euAP3 lineage and included a distinctive PI-derived and euAP3 motifs at the C-terminal domain. Subcellular localization of EjAP3 was determined to be in the nucleus. Expression analysis suggested that EjAP3 expression was restricted only in petals and stamens, but not in sepals and carpels. Importantly, during the floral development, EjAP3 expression level was the highest at the stage of visible floral bud. Furthermore, ectopic expression of EjAP3 in Arabidopsis ap3-3 mutant rescued the second whorl petals and the third whorl stamens. The expression pattern and function characterization of EjAP3 contribute to better understand the roles of AP3 orthologs in Eriobotrya.

17.
BMJ Open ; 9(12): e028518, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796472

RESUMO

INTRODUCTION: Portal hypertension (PH) is a severe disease with a poor outcome. Hepatic venous pressure gradient (HVPG), the current gold standard to detect PH, is available only in few hospitals due to its invasiveness and technical difficulty. This study aimed to establish and assess a novel model to calculate HVPG based on biofluid mechanics. METHODS AND ANALYSIS: This is a prospective, randomised, non-controlled, multicentre trial. A total of 248 patients will be recruited in this study, and each patient will undergo CT, blood tests, Doppler ultrasound and HVPG measurement. The study consists of two independent and consecutive cohorts: original cohort (124 patients) and validation cohort (124 patients). The researchers will establish and improve the HVPG using biofluid mechanics (HVPGBFM)model in the original cohort and assess the model in the validation cohort. ETHICS AND DISSEMINATION: The study was approved by the Scientific Research Projects Approval Determination of Independent Ethics Committee of Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (approval number 2017-430 T326). Study findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03470389.

18.
Mol Genet Genomic Med ; : e1102, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31859449

RESUMO

BACKGROUND: The role of meteorin (METRN) in colorectal cancer has not been reported previously. We aimed to explore the relationship between METRN and colorectal cancer (CRC) prognosis. METHODS: Data were retrieved from the Gene Expression Omnibus database. Gene expression values were log2 transformed and normalized by quantile normalization. Missing values were imputed with the R impute package. Differentially expressed genes were analyzed using the R limma package. METRN expression was compared between normal and CRC tissues and among different stages and subtypes of CRC. We assessed the relationship between METRN and KRAS/BRAF mutations in CRC. Five-year overall (OS), disease-free (DFS), and disease-specific survival (DSS) rates were determined by Kaplan-Meier analysis and analyzed by log-rank test. RESULTS: METRN was expressed at a higher level in CRC (p = .0011) than in normal tissues, especially in advanced stages (p = .0343). METRN expression levels were higher in the MSI (dMMR) subtype (p < .001) and usually with BRAF mutations (p < .0001). METRN overexpression was associated with poor prognosis and low OS (p = .01014), DFS (p = .0146), and DSS (p < .0001) rates. CONCLUSION: METRN overexpression is a predictive factor for poor prognosis in patients with CRC.

19.
J Asian Nat Prod Res ; : 1-10, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31773971

RESUMO

Gramine can be intelligently and efficiently supplied with N, N-dimethylamino group and then reacted with the corresponding sulfonyl chlorides to synthesize N, N-dimethylarylsulfonamides. We herein designed and controlled synthesis of N, N-dimethylarylsulfonamide derivatives, and first reported the results of the nematicidal activity of 15 title compounds 3a-o against Meloidogyne incongnita in vitro, respectively. Among all of the title derivatives, compounds 3a, 3c, 3k, and 3o exhibited potent nematicidal activity with median lethal concentration (LC50) values ranging from 0.22 to 0.26 mg/L. Most noteworthy, N, N-dimethyl-4-methoxyphenylsulfonamide (3c) and N, N-dimethyl-8-quinolinesulfonamide (3o) showed the best promising and pronounced nematicidal activity, with LC50 values of 0.2381 and 0.2259 mg/L, respectively.

20.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 339-345, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701719

RESUMO

OBJECTIVE: To understand and analyze the rules of endurance exercise on the cerebral cortex adaptive mechanism in aged rats. METHODS: In this study, 3-month-old (n=20), 13-month-old (n=24) and 23-month-old (n=24) specific-pathogen free (SPF) male Sprague-Dawley Rat (SD) rats were divided into young (Y-SED), middle-aged (M-SED) and old-aged (O-SED) sedentary control group, and the corresponding Y-EX, M-EX and O-EX in the endurance exercise runner group. The 10-weeks of regular moderate-intensity aerobic exercise intervention were carried out in the endurance exercise runner group. The exercise mode is treadmill exercise (slope 0), and the exercise intensity gradually increases from 60%~65% of the maximum oxygen consumption (V·O2max) to 70%~75%, and the exercise time is 10 weeks. Hematoxylin and eosin (HE) staining was used to detect age-related morphological changes. The expressions of superoxide dismutase(SOD) and brain-derived neurotrophic factor (BDNF) and the expressions of synapsin 1 (SYN1) and Ca2+/calmodulin- dependent protein kinases IIα (CaMK IIα) / AMP-activated protein kinase α1(AMPKα1) / mammalian target of rapamycin (mTOR) pathway -related genes were detected. RESULTS: The cerebral cortex structure of the rats in each group showed age-related aging changes, the expression of SOD in the cortex showed a gradual decline, the expression of BDNF showed an age-increasing trend, and the expression levels of SYN1 and CaMK IIα were increased with age. The changes in AMPKα1 and SirT2 and IP3R, AKT1 and mTOR mRNA levels were increased slightly in middle-aged rats and decreased in aged rats. Compared with the rats in each sedentary control group, the nucleus of the cerebral cortex was tightly arranged and the number of nuclei observed under the microscope was increased significantly in each exercise group. Exercise promoted the expressions of SOD, BDNF and synaptophysin SYN1 in the cortex of rats, and the expression levels of SOD and BDNF in aged rats were up-regulated significantly (P< 0.01). The expression level of SYN1 in rats was up-regulated significantly (P<0.05) in the young and aged rats. The expression of CaMK IIα in the cortex of middle-aged and aged rats was up-regulated (P<0.01), while the expression level of CaMK IIα in young rats was down-regulated (P<0.01). Exercise could up-regulate the expression level of AMPKα1 in the cortex of young rats (P< 0.05), but not in middle-aged and old-age rats. Exercise could up-regulate the expression of SirT2 in the cortex of rats in all age groups (P<0.05). Exercise up-regulated the expression of phosphoinositide 3-kinase (IP3R)/ protein kinase B 1(AKT1) /mTOR in the cortex of rats, among which young IP3R was significantly up-regulated (P<0.01) in the young group, mTOR was significantly up-regulated in young and middle-aged group (P<0.01), and mTOR was also significantly up-regulated in the aged group (P<0.05). CONCLUSION: Endurance exercise up-regulates BDNF expression, regulates CaMKIIα signaling, activates AMPK signaling pathway and IP3R / AKT1 / mTOR signaling pathway, and improves synaptic plasticity in the cortex.


Assuntos
Córtex Cerebral/fisiologia , Plasticidade Neuronal , Condicionamento Físico Animal , Resistência Física , Transdução de Sinais , Fatores Etários , Animais , Masculino , Ratos , Ratos Sprague-Dawley
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