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21.
Dr. Anders Højgaard Hansen Henriette B. Christensen Dr. Sunil K. Pandey Dr. Eugenia Sergeev Alice Valentini Julia Dunlop Domonkos Dedeo Simone Fratta Dr. Brian D. Hudson Prof. Graeme Milligan Prof. Trond Ulven Prof. Elisabeth Rexen Ulven 《ChemMedChem》2021,16(21):3326-3341
Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties. 相似文献
22.
Ashish Ganvir Mohit Gupta Nitish Kumar Nicolaie Markocsan 《Ceramics International》2021,47(1):272-283
This paper investigates the influence of suspension characteristics on microstructure and performance of suspensions plasma sprayed (SPS) thermal barrier coatings (TBCs). Five suspensions were produced using various suspension characteristics, namely, type of solvent and solid load content, and the resultant suspensions were utilized to deposit five different TBCs under identical processing conditions. The produced TBCs were evaluated for their performance i.e. thermal conductivity, thermal cyclic fatigue (TCF) and thermal shock (TS) lifetime. This experimental study revealed that the differences in the microstructure of SPS TBCs produced using varied suspensions resulted in a wide-ranging overall TBC performance. All TBCs exhibited thermal conductivity lower than 1 W/(m. K) except water-ethanol mixed suspension produced TBC. The TS lifetime was also affected to a large extent where 10 wt % solid loaded ethanol and 25 wt % solid loaded water suspensions produced TBCs exhibited the highest and the lowest lifetime, respectively. On the contrary, TCF lifetime was not as significantly affected as thermal conductivity and TS lifetime, and all ethanol suspensions showed marginally better TCF lifetime than water and ethanol-water mixed suspensions deposited TBCs. 相似文献
23.
Elisa Mascolo Francesco Liguori Lorenzo Stufera Mecarelli Noemi Amoroso Chiara Merigliano Susanna Amadio Cinzia Volont Roberto Contestabile Angela Tramonti Fiammetta Vernì 《International journal of molecular sciences》2021,22(2)
Maturity-onset diabetes of the young (MODY) type 2 is caused by heterozygous inactivating mutations in the gene encoding glucokinase (GCK), a pivotal enzyme for glucose homeostasis. In the pancreas GCK regulates insulin secretion, while in the liver it promotes glucose utilization and storage. We showed that silencing the Drosophila GCK orthologs Hex-A and Hex-C results in a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin producing cells (IPCs) whereas Hex-C is specifically expressed in the fat body. We showed that Hex-A is essential for insulin secretion and it is required for Hex-C expression. Reduced levels of either Hex-A or Hex-C resulted in chromosome aberrations (CABs), together with an increased production of advanced glycation end-products (AGEs) and reactive oxygen species (ROS). This result suggests that CABs, in GCK depleted cells, are likely due to hyperglycemia, which produces oxidative stress through AGE metabolism. In agreement with this hypothesis, treating GCK-depleted larvae with the antioxidant vitamin B6 rescued CABs, whereas the treatment with a B6 inhibitor enhanced genomic instability. Although MODY-2 rarely produces complications, our data revealed the possibility that MODY-2 impacts genome integrity. 相似文献
24.
Mohammad Bani Ismail Peramaiyan Rajendran Hamad Mohammed AbuZahra Vishnu Priya Veeraraghavan 《International journal of molecular sciences》2021,22(8)
Doxorubicin increases endothelial permeability, hence increasing cardiomyocytes’ exposure to doxorubicin (DOX) and exposing myocytes to more immediate damage. Reactive oxygen species are major effector molecules of doxorubicin’s activity. Mangiferin (MGN) is a xanthone derivative that consists of C-glucosylxanthone with additional antioxidant properties. This particular study assessed the effects of MGN on DOX-induced cytotoxicity in human umbilical vein endothelial cells’ (HUVECs’) signaling networks. Mechanistically, MGN dramatically elevated Nrf2 expression at both the messenger RNA and protein levels through the upregulation of the PI3K/AKT pathway, leading to an increase in Nrf2-downstream genes. Cell apoptosis was assessed with a caspase-3 activity assay, transferase-mediated dUTP-fluorescein nick end labeling (TUNEL) staining was performed to assess DNA fragmentation, and protein expression was determined by Western blot analysis. DOX markedly increased the generation of reactive oxygen species, PARP, caspase-3, and TUNEL-positive cell numbers, but reduced the expression of Bcl-2 and antioxidants’ intracellular concentrations. These were effectively antagonized with MGN (20 μM), which led to HUVECs being protected against DOX-induced apoptosis, partly through the PI3K/AKT-mediated NRF2/HO-1 signaling pathway, which could theoretically protect the vessels from severe DOX toxicity. 相似文献
25.
With the increase of industrialization and urbanization, humankind faces massive oil-based pollution due to tanker accidents, human error, and natural disasters. For this, hydrophobic sorbents are fabricated and their applications for the removal of oil from polluted water sources are investigated. These hydrophobic sorbents are prepared by the condensation reaction of poly(dimethylsiloxane) and tris[3-(trimethoxysilyl)propyl]isocyanurate cross-linker via bulk polymerization. The obtained sorbents exhibit high oil sorption capacity, fast absorption–desorption kinetics, and great reusability. Moreover, they can selectively absorb oil from the water surface, thus making them practical for water clean-up applications. 相似文献
26.
Dr. Md Kausar Raza Aisha Noor Dr. Paresh Kumar Samantaray 《Chembiochem : a European journal of chemical biology》2021,22(23):3270-3272
Individually, photoredox catalysis (PC) and photodynamic therapy (PDT) are well-established concepts that have experienced a remarkable resurgence in recent years, leading to significant progress in organic synthesis for PC and clinical approval of anticancer drugs for PDT. But, very recently, new photoredox catalyst systems based on Ir(III) and Ru(II) complexes have garnered significant interest because they can simultaneously be used as PDT agents apart from their demonstrated PC activity. This highlight discusses the unique PC behavior of emerging Ir(III)- and Ru(II)-based systems while also examining their potential PDT activity in cancer treatment. 相似文献
27.
Daisuke Yamanaka Suzuka Kurita Yuka Hanayama Yoshiyuki Adachi 《International journal of molecular sciences》2021,22(4)
β-Glucan is widely distributed in various plants and microorganisms and is composed of β-1,3-linked d-glucose units. It may have a branched short or long side chain of glucose units with β-1,6- or β-1,4-linkage. Numerous studies have investigated different β-glucans and revealed their bioactivities. To understand the structure-function relationship of β-glucan, we constructed a split-luciferase complementation assay for the structural analysis of long-chain β-1,6-branched β-1,3-glucan. The N- and C-terminal fragments of luciferase from deep-sea shrimp were fused to insect-derived β-1,3-glucan recognition protein and fungal endo-β-1,6-glucanase (Neg1)-derived β-1,6-glucan recognition protein, respectively. In this approach, two β-glucan recognition proteins bound to β-glucan molecules come into close proximity, resulting in the assembly of the full-length reporter enzyme and induction of transient luciferase activity, indicative of the structure of β-glucan. To test the applicability of this assay, β-glucan and two β-glucan recognition proteins were mixed, resulting in an increase in the luminescence intensity in a β-1,3-glucan with a long polymer of β-1,6-glucan in a dose-dependent manner. This simple test also allows the monitoring of real-time changes in the side chain structure and serves as a convenient method to distinguish between β-1,3-glucan and long-chain β-1,6-branched β-1,3-glucan in various soluble and insoluble β-glucans. 相似文献
28.
采用溶胶-凝胶法制备CuO-SiO2复合气凝胶,通过在气凝胶孔道内填充TiCl4,然后将其气相水解,得到了在CuO-SiO2气凝胶表面生长了高结晶度的TiO2纳米纤维(CuO-SiO2@TiO2),纤维直径~16 nm.通过XPS、UPS、UV-Vis DRS、荧光光谱(PL)等表征了材料的结构及光电性能.结果表明,制备的CuO-SiO2@TiO2对可见光有明显吸收,且荧光强度较商用TiO2(P25)大幅降低,光生电子-空穴对更加稳定.再在纳米纤维上负载CuO,所得CuO-SiO2@TiO2/CuO在可见光区的荧光强度进一步增强.以300 W氙灯为光源,分别以CuO-SiO2@TiO2及CuO-SiO2@TiO2/CuO为催化剂,无牺牲剂条件下光催化还原CO2,4 h后甲醇产率分别为1304.0及1589.0μmol/g-cat,转换频率(TOF)分别为0.038及0.046 h–1.循环实验表明,纳米纤维具有较好的光催化稳定性,经过4次光催化循环实验后,CuO-SiO2@TiO2/CuO的保留率~94%,甲醇产率可达1472.0μmol/g-cat,TOF为0.042 h–1. 相似文献
29.
气藏平均地层压力跟踪计算新方法 总被引:1,自引:0,他引:1
平均地层压力是产能评价和动态分析的基础,准确、快速获取平均地层压力对高效开发气藏意义重大。基于地层压力随时间变化的规律,分析了平均地层压力的变化规律。研究结果表明:平均地层压力等效点仅随时间发生改变,平均地层压力的下降速率等于或者近似等于井底流压的下降速率。从封闭弹性驱动气藏的物质平衡方程出发,考虑偏差系数和井底流压随平均地层压力的变化,推导建立了平均地层压力跟踪计算新方法,根据生产数据可迭代计算平均地层压力。方法验证结果显示,采气速度和采出程度共同影响模型的计算结果。应用实例表明,跟踪计算法与压力恢复试井和物质平衡法之间的相对误差均较小,满足工程计算精度要求,且跟踪计算法不需依托生产测试数据,节约了测试费用,避免了测试占产。 相似文献
30.