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1.
    
Thoracic pair of mammary glands from steroid hormone-pretreated mice respond to hormones structurally and functionally in organ culture. A short exposure of glands for 24 h to 7,12 Dimethylbenz(a)anthracene (DMBA) during a 24-day culture period induced alveolar or ductal lesions. Methods: To differentiate the functional significance of ERα and ERβ, we employed estrogen receptor (ER) knockout mice. We compared the effects of DMBA on the development of preneoplastic lesions in the glands in the absence of ERα (αERKO) and ERβ (βERKO) using an MMOC protocol. Glands were also subjected to microarray analyses. We showed that estradiol can be replaced by EGF for pretreatment of mice. The carcinogen-induced lesions developed under both steroids and EGF pretreatment protocols. The glands from αERKO did not develop any lesions, whereas in βERKO mice in which ERα is intact, mammary alveolar lesions developed. Comparison of microarrays of control, αERKO and βERKO mice showed that ERα was largely responsible for proliferation and the MAP kinase pathways, whereas ERβ regulated steroid metabolism-related genes. The results indicate that ERα is essential for the development of precancerous lesions. Both subtypes, ERα and Erβ, differentially regulated gene expression in mammary glands in organ cultures.  相似文献   

2.
    
To ascertain the role of Zn(II) as an allosteric modulator on P2X4R, QM/MM molecular dynamic simulations were performed on the WT and two P2X4R mutants suggested by previous electrophysiological data to affect Zn(II) binding. The Gibbs free energy for the reduction of the putative P2X4R Zn(II) binding site by glutathione was estimated at −22 kcal/mol. Simulations of the WT P2X4R head domain revealed a flexible coordination sphere dominated by an octahedral geometry encompassing C126, N127, C132, C149, C159 and a water molecule. The C132A mutation disrupted the metal binding site, leading to a coordination sphere with a majority of water ligands, and a displacement of the metal ion towards the solvent. The C132A/C159A mutant exhibited a tendency towards WT-like stability by incorporating the R148 backbone to the coordination sphere. Thus, the computational findings agree with previous experimental data showing Zn(II) modulation for the WT and C132A/C159A variants, but not for the C132A mutant. The results provide molecular insights into the nature of the Zn(II) modulation in P2X4R, and the effect of the C132A and C132A/C159A mutations, accounting for an elusive modulation mechanism possibly occurring in other extracellular or membrane protein.  相似文献   

3.
    
Parkinson’s disease (PD) is a socially significant disease, during the development of which oxidative stress and inflammation play a significant role. Here, we studied the neuroprotective effects of four Kunitz-type peptides from Heteractis crispa and Heteractis magnifica sea anemones against PD inductors. The peptide HCIQ1c9, which was obtained for the first time, inhibited trypsin less than other peptides due to unfavorable interactions of Arg17 with Lys43 in the enzyme. Its activity was reduced by up to 70% over the temperature range of 60–100 °C, while HCIQ2c1, HCIQ4c7, and HMIQ3c1 retained their conformation and stayed active up to 90–100 °C. All studied peptides inhibited paraquat- and rotenone-induced intracellular ROS formation, in particular NO, and scavenged free radicals outside the cells. The peptides did not modulate the TRPV1 channels but they affected the P2X7R, both of which are considered therapeutic targets in Parkinson’s disease. HMIQ3c1 and HCIQ4c7 almost completely inhibited the ATP-induced uptake of YO-PRO-1 dye in Neuro-2a cells through P2X7 ion channels and significantly reduced the stable calcium response in these cells. The complex formation of the peptides with the P2X7R extracellular domain was determined via SPR analysis. Thus, these peptides may be considered promising compounds to protect neuronal cells against PD inductors, which act as ROS production inhibitors and partially act as ATP-induced P2X7R activation inhibitors.  相似文献   

4.
Blends of either of two different poly(phenylene oxide) (PPO) derivatives with poly(2-vinylnaphthalene) (P2VN) were prepared by casting from chloroform. The content of P2VN in the blends ranged from 0 to 25 wt % for each PPO derivative. Two kinds of PPO derivatives, p–t-butylbenzoyl poly(phenylene oxide) (p–t-BB-PPO) and benzoyl poly(phenylene oxide) (B-PPO), were used. The effects of the addition of P2VN to PPO derivatives were investigated by their thermal stability, light-resistance, and tensile properties. Even though the addition of P2VN to the PPO derivatives decrease the mechanical properties, the radiation resistance was improved. The radiation resistance and tensile properties of B-PPO and its blends with P2VN were higher than those of the p–t-BB-PPO and its blends with P2VN. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 73: 1697–1705, 1999  相似文献   

5.
    
Increasing evidence has shown P2Y12 inhibitor monotherapy is a feasible alternative treatment for patients after percutaneous coronary intervention (PCI) with stent implantation in the modern era. However, patients with diabetes mellitus (DM) have a higher risk of ischemic events and more complex coronary artery disease. The purpose of this study is to evaluate the efficacy and safety of this novel approach among patients with DM and those without DM. We conducted a systematic review and meta-analysis of randomized controlled trials that compared P2Y12 inhibitor monotherapy with 12 months of dual antiplatelet therapy (DAPT) in patients who underwent PCI with stent implantation. PubMed, Embase, Cochrane library database, ClinicalTrials.gov, and three other websites were searched for our data from the earliest report to January 2022. The primary efficacy outcome was major adverse cardiovascular and cerebrovascular events (MACCE): a composite of all-cause mortality, myocardial infarction, stent thrombosis, and stroke. The primary safety outcome was major or minor bleeding events. The secondary endpoint was net adverse clinical events (NACE) which are defined as a composite of major bleeding and adverse cardiac and cerebrovascular events. A total of four randomized controlled trials with 29,136 patients were included in our meta-analysis. The quantitative analysis showed a significant reduction in major or minor bleeding events in patients treated with P2Y12 inhibitor monotherapy compared to standard DAPT (OR: 0.68, 95% CI: 0.46–0.99, p = 0.04) without increasing the risk of MACCE (OR: 0.96, 95% CI: 0.85–1.09, p = 0.50). The number of NACE was significantly lower in the patients treated with P2Y12 inhibitor monotherapy (OR: 0.84, 95% CI: 0.72–0.97, p = 0.019). In DM patients, P2Y12 inhibitor monotherapy was associated with a lower risk of MACCE compared to standard DAPT (OR: 0.85, 95% CI: 0.74–0.98, p = 0.02). Furthermore, P2Y12 inhibitor monotherapy was accompanied by a favorable reduction in major or minor bleeding events (OR: 0.80, 95% CI: 0.64–1.05, p = 0.107). In non-DM patients, P2Y12 inhibitor monotherapy showed a significant reduction in major or minor bleeding events (OR: 0.58, 95% CI: 0.38–0.88, p = 0.01), but without increasing the risk of MACCE (OR: 0.99, 95% CI: 0.82–1.19, p = 0.89). Based on these findings, P2Y12 inhibitor monotherapy could significantly decrease bleeding events without increasing the risk of stent thrombosis or myocardial infarction in the general population. The benefit of reducing bleeding events was much more significant in non-DM patients than in DM patients. Surprisingly, P2Y12 inhibitor monotherapy could lower the risk of MACCE in DM patients. Our study supports that P2Y12 inhibitor monotherapy is a promising alternative choice of medical treatment for patients with DM undergoing PCI with stent implantation in the modern era.  相似文献   

6.
针对苯乙烯（St）的常温聚合速率缓慢影响了其在常温聚合诱导自组装（PISA）中的应用问题,提出了一种无需添加光引发剂或光催化剂,以蓝光LED为光源,聚2-乙烯基吡啶（P2VP）为大分子链转移剂,常温下在甲醇中实现St的PISA的方法。通过可见光引发的PISA制备了聚2-乙烯基吡啶-b-聚苯乙烯（P2VP-b-PSt）纳米材料,考察了St/P2VP的比例、聚合时间及P2VP的链长对聚集体形貌的影响,结果表明,当P2VP的分子量为4000、St/P2VP的摩尔比从400/1变化到4000/1、聚合时间从3h变化到24h,均可以实现聚集体从球形胶束到囊泡的转变;当P2VP的分子量为8300时,仅能得到球形胶束。  相似文献   

7.
    
We investigate the thermal and electrochemical properties of xFe2O3-(100-x) P2O5 glass (x = 20, 30, 40, and 50 mol%) and 50Fe2O3-50P2O5 (50FeP) glass-ceramics as anodes for lithium-ion batteries (LiBs). The results show that both the glass transition temperature and the energy bandgap monotonically decrease with the increasing Fe2O3 while a critical Fe2O3 content of 30 mol% is found to give glass the highest thermal stability, the largest capacity at 1 Ag-1, and the lowest charge-transfer resistance before cycling. Moreover, Fe3(P2O7)2 crystals formed during heat treatment in 50FeP glass effectively enhances the electrochemical properties. The optimum heat treatment condition for 50FeP glass is found at 1033 K for 4 h, that is, 1033 K-4 h sample enables a reversible capacity of 237 mA h g−1 at the end of 1000 cycles at 1 Ag-1, which is more than 1.5 times higher than that of the 50FeP glass-based anode. These findings suggest that the Fe2O3-P2O5 glass-ceramics hold significant potential for the effective development of new types of glass anodes for future advanced LiBs.  相似文献   

8.
对2一甲基咪唑为反应底物制备1,1一二氨基一2,2．二硝基乙烯(FOx一7)的合成方法进行了实验研究,找到了一种新的合成FOx．7的方法,该方法首次采用低碳有机羧酸与硝化中间体2一(二硝基亚甲基)．4,5．咪唑烷二酮l的反应实现FOx一7的合成,对产物结构进行了表征并对反应奈件进行了优化。开环试剂为甲酸时,最优条件下两步反应(收率分别为20．3％和95．3％)的总收率约为19．3％,与氨水开环法(约13、1％)相比收率有较大幅度提高,通过控制反应时间和结晶时间可对FOx．7的颗粒度进行控制,同时该方法也是制备大颗粒和不同形貌特征FOx一7的有效方法。对开环反应机理进行了探讨,  相似文献   

9.
    
Mucin 7 (encoded byMUC7) is a human salivary protein that has a role in the natural immune system. Fragments of mucin 7 exhibit antimicrobial activity against bacteria and yeast. Although the antimicrobial properties of peptides have been known and studied for decades, the exact mechanism of action of antimicrobial peptides (AMPs) is still unclear. It is known that some AMPs require divalent metal ions to activate their activity. Herein, we investigated three 15-mer MUC7 peptides, one of which (mother peptide, sequence, L3) is a synthetic analog of a fragment naturally excised from MUC7 (with His3, His8, and His 14) and its two structural analogs, containing only two histidine residues, His3, His13 and His8, His13 (L2 and L1, respectively). Since there is a correlation between lipophilicity, the presence of metal ions (such as Cu(II) and Zn(II)) and antimicrobial activity of AMP, antimicrobial properties of the studied peptides, as well as their complexes with Cu(II) and Zn(II) ions, were tested for activity against Gram-positive (Enterococcus faecalis, Staphylococcus epidermidis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and fungi (Candida albicans). The results were correlated with their lipophilicity. Coordination and thermodynamic studies (potentiometry, UV-Vis, CD) revealed the formation of mainly mononuclear complexes in solution for all studied systems with different stability in the physiological pH range.  相似文献   

10.
    
Fumonisins are protein serine/threonine phosphatase inhibitors and potent inhibitors of sphingosine N-acyltransferase (ceramide synthase) disrupting de novo sphingolipid biosynthesis. The experiment was conducted to evaluate the effects of fumonisins (FB) exposure from the 7th day of pregnancy to parturition on offspring bone development. The rats were randomly allocated to either a control group (n = 6), not treated with FBs, or to one of the two groups intoxicated with FBs (either at 60 mg FB/kg b.w. or at 90 mg FB/kg b.w. Numerous negative, offspring sex-dependent effects of maternal FB exposure were observed with regards to the histomorphometry of trabecular bone. These effects were due to FB-inducted alterations in bone metabolism, as indicated by changes in the expression of selected proteins involved in bone development: tissue inhibitor of metalloproteinases 2 (TIMP-2), matrix metalloproteinase 8 (MMP-8), matrix metalloproteinase 13 (MMP-13), and vascular endothelial growth factor (VEGF). The immunolocalization of MMPs and TIMP-2 was performed in trabecular and compact bone, as well as articular and growth plate cartilages. Based on the results, it can be concluded that the exposure of pregnant dams to FB negatively affected the expression of certain proteins responsible for bone matrix degradation in newborns prenatally exposed to FB in a dose- and sex-dependent manner.  相似文献   

11.
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12.
    
To improve the energy-to-CH4 efficiency and enhance renewable power utilization, we investigate direct Power-to-Methane at low inlet H2 content (25 vol%) in solid oxide electrolysis cell (SOEC). The synergy of the pressurized operation and the electricity input effectively enhances CH4 yield by one-order of magnitude from 2.8% to 28.7% and the CO2-to-CH4 ratio from 4.4% to 39.5% in the H2-reduced case, where the ratio of H2 consumption to total energy consumption decreases to 41% and the energy-to-CH4 efficiency increases to 53%. We develop a multiphysics tubular SOEC model to understand the intrinsic coupling between electrochemistry and heterogeneous catalytic chemistry. From the perspective of performance enhancement, geometry optimization, and thermal design, inhibiting CH4 production in the inlet gas-controlled zone and promoting CH4 production synergistically in both the electrochemistry-controlled zone and the temperature-controlled zone is the key to improve the energy-to-CH4 efficiency.  相似文献   

13.
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14.
    
A MgCl2‐supported catalyst containing diisobutyl phthalate (DIBP) and 2,4‐pentadiol dibenzoate (PDDB) as internal donors was prepared. Propylene polymerizations were carried out using the catalyst in the absence or presence of an external donor. The resulting polymers were characterized by 13C‐NMR, crystallization analysis fraction (CRYSTAF) and gel permeation chromatography (GPC). The performance of the catalyst was compared with that of other catalysts containing donor‐free, DIBP and PDDB as internal donors respectively. The results demonstrated that the catalyst containing mixed internal donors not only had high activity and stereospecificity but also produced the polymer with relatively broad molecular weight distribution and the highest [mmmm] value. 13C‐NMR analysis results indicated that strongly coordinating donors gave more stereoregular polymers, which was further confirmed by CRYSTAF data. The effects of mixed internal donors on the catalyst properties were discussed systematically. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011  相似文献   

15.
4－（对甲氧基苯基）－7－甲氧基－1－羟基－3－萘甲酸是一种新药物的中间体,它由茴香酸和茴香醚经Friedel-Crafts（付克）反应;再与丁二酸二乙酯在叔丁醇钾的碱中缩合,脱水;然后经分子内的付克反应成环;后者在相转移催化剂（PTC）存在下水解得目标产物,总产率达41．9％,产品纯度达99．7％。  相似文献   

16.
    
An NAD(P)H oxidase‐like activity was found in semisynthetic flavoadducts, prepared from an aldehyde derivative of riboflavin and commercial poly(vinylalcohol) (PVA), previously grafted with aminopropyl side chains. Both water‐soluble and water‐insoluble beaded preparations were obtained. The products showed a noticeable NAD(P)H oxidase‐like activity, converting the nucleotide substrate to its oxidized counterpart NAD(P)+ at the expense of molecular oxygen, the latter being reduced to hydrogen peroxide. In contrast to some “true” β‐NAD(P)H oxidases, the PVA adducts do not require the presence of additional flavin adenine dinucleotide (FAD) to work; some properties of the flavoadducts were studied that make these flavoadducts good candidates for technological applications. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 2471–2477, 2002  相似文献   

17.
    
Poly (4‐vinylpyridine) (P4VP) brushes had been prepared by the surface‐initiated nitroxide‐mediated radical polymerization of 4‐VP on the surface of 3‐methacryloxyproyltrimethoxysilane (3‐MPS)‐modified magnetite nanoparticles with an average diameter of 30 nm. The grafting polymerization was accomplished by nitroxide‐mediated polymerization of 4‐VP, using 4‐hydroxyl‐2,2,6,6‐tetramethyl‐1‐piperidinyl‐oxy (HTEMPO·) free radical as capping agent and benzoyl peroxide (BPO) as initiator. X‐ray photoelectron spectra (XPS) measurement demonstrated that the alkoxysilane initiator layer had formed on the magnetite surface. Gel permeation chromatograph analysis and XPS measurement suggested that the amount of grafted P4VP increases with increasing grafting time. The amount of P4VP grafted on the surface could be determined to be 0.09 chains/nm2 by thermogravimetric analysis. The P4VP‐grafted magnetite particles exhibited the characteristics of multidomain system, distinct from the single domain attributes of the pure magnetite particles. Atomic force‐microscopy analysis revealed the diameter of the grafted P4VP magnetic latex particles is in the range of 120 nm to 150 nm. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011  相似文献   

18.
    
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19.
以H_6P_2Mo_(18)O_(62)、[Ni(2,2'-bipy)_3]Cl_2·5.5H_2O为原料,通过化学共沉淀法制备[Ni(2,2'-bipy)_3]_3(P_2Mo_(18)O_(62))复合材料,采用FT-IR、SEM、TG、BET等手段进行表征,并研究其对亚甲基蓝(MB)溶液的吸附性能。探讨了pH、初始浓度、温度等条件对MB溶液吸附效果的影响。结果表明,将H_6P_2Mo_(18)O_(62)与[Ni(2,2'-bipy)_3]Cl_2·5.5H_2O进行复合形成复合物[Ni(2,2'-bipy)_3]_3(P_2Mo_(18)O_(62))后,可有效克服其水溶性,大大提高了其液相吸附能力,且温度对其吸附性能影响不大。从实验结果可知,复合物对MB溶液的吸附分别符合Langmuir等温吸附模型和拟二级动力学模型。热力学参数ΔG~00、ΔH~00和ΔS~00,表明该吸附剂对亚甲基蓝的吸附是自发且放热的,且对其他阳离子染料罗丹明B也有较好的吸附效果。  相似文献   

20.
A series of water insoluble poly[(2-ethyl-2-oxazoline)-ran-(2-nonyl-2-oxazoline)] amphiphilic copolymers was synthesized and their solubility properties in the presence of different supramolecular host molecules were investigated. The resulting polymer-cavitand assemblies exhibited a thermoresponsive behavior that could be modulated by variation of the copolymer composition and length. Interestingly, the large number of hydrophobic nonyl units across the polymer chain induced the formation of kinetically-trapped nanoparticles in solution. These nanoparticles further agglomerate into larger aggregates at a temperature that is dependent on the polymer composition and the cavitand type and concentration. The present research expands the understanding on the supramolecular interactions between water insoluble copolymers and supramolecular host molecules.  相似文献   

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