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1.
Jingwei Shi Xujun Song Benno Traub Michael Luxenhofer Marko Kornmann 《International journal of molecular sciences》2021,22(6)
Interleukin (IL)-4 and IL-13 are known as pleiotropic Th2 cytokines with a wide range of biological properties and functions especially in immune responses. In addition, increasing activities have also been determined in oncogenesis and tumor progression of several malignancies. It is now generally accepted that IL-4 and IL-13 can exert effects on epithelial tumor cells through corresponding receptors. Type II IL-4 receptor (IL-4Rα/IL-13Rα1), predominantly expressed in non-hematopoietic cells, is identified to be the main target for both IL-4 and IL-13 in tumors. Moreover, IL-13 can also signal by binding to the IL-13Rα2 receptor. Structural similarity due to the use of the same receptor complex generated in response to IL-4/IL-13 results in overlapping but also distinct signaling pathways and functions. The aim of this review was to summarize knowledge about IL-4 and IL-13 and their receptors in pancreatic cancer in order understand the implication of IL-4 and IL-13 and their receptors for pancreatic tumorigenesis and progression and for developing possible new diagnostic and therapeutic targets. 相似文献
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3.
Corey Andrews Yiting Xu Michael Kirberger Jenny J. Yang 《International journal of molecular sciences》2021,22(1)
Calmodulin (CaM) is an important intracellular protein that binds Ca2+ and functions as a critical second messenger involved in numerous biological activities through extensive interactions with proteins and peptides. CaM’s ability to adapt to binding targets with different structures is related to the flexible central helix separating the N- and C-terminal lobes, which allows for conformational changes between extended and collapsed forms of the protein. CaM-binding targets are most often identified using prediction algorithms that utilize sequence and structural data to predict regions of peptides and proteins that can interact with CaM. In this review, we provide an overview of different CaM-binding proteins, the motifs through which they interact with CaM, and shared properties that make them good binding partners for CaM. Additionally, we discuss the historical and current methods for predicting CaM binding, and the similarities and differences between these methods and their relative success at prediction. As new CaM-binding proteins are identified and classified, we will gain a broader understanding of the biological processes regulated through changes in Ca2+ concentration through interactions with CaM. 相似文献
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5.
Viktoria M. S. Kjær Loukas Ieremias Dr. Viktorija Daugvilaite Dr. Michael Lückmann Prof. Thomas M. Frimurer Prof. Trond Ulven Prof. Mette M. Rosenkilde Dr. Jon Våbenø 《ChemMedChem》2021,16(17):2623-2627
The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca2+ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch. 相似文献
6.
Valentin Jolivet Yann Morizet Jonathan Hamon Michael Paris Tomo Suzuki-Muresan 《Journal of the American Ceramic Society》2021,104(3):1360-1369
The glass transition temperature (Tg) is a key parameter to investigate for application in nuclear waste immobilization in borosilicate glasses. Tg for several glasses containing iodine (I) has been measured in order to determine the I effect on Tg. Two series of glass composition (ISG and NH) containing up to 2.5 mol% I and synthesized under high pressure (0.5 to 1.5 GPa) have been investigated using differential scanning calorimetry (DSC). The I local environment in glasses has been determined using X-ray photoelectron spectroscopy and revealed that I is dissolved under its iodide form (I−). Results show that Tg is decreased with the I addition in the glass in agreement with previous results. We also observed that this Tg decrease is a strong function of glass composition. For NH, 2.5 mol% I induces a decrease of 24°C in Tg, whereas for ISG, 1.2 mol% decreases the Tg by 64°C. We interpret this difference as the result of the I dissolution mechanism and its effect on the polymerization of the boron network. The I dissolution in ISG is accompanied by a depolymerization of the boron network, whereas it is the opposite in NH. Although ISG corresponds to a standardized glass, for the particular case of I immobilization it appears less adequate than NH considering that the decrease in Tg for NH is small in comparison to ISG. 相似文献
7.
Matej Vizovisek Dragana Ristanovic Stefano Menghini Michael G. Christiansen Simone Schuerle 《International journal of molecular sciences》2021,22(5)
In recent decades, dysregulation of proteases and atypical proteolysis have become increasingly recognized as important hallmarks of cancer, driving community-wide efforts to explore the proteolytic landscape of oncologic disease. With more than 100 proteases currently associated with different aspects of cancer development and progression, there is a clear impetus to harness their potential in the context of oncology. Advances in the protease field have yielded technologies enabling sensitive protease detection in various settings, paving the way towards diagnostic profiling of disease-related protease activity patterns. Methods including activity-based probes and substrates, antibodies, and various nanosystems that generate reporter signals, i.e., for PET or MRI, after interaction with the target protease have shown potential for clinical translation. Nevertheless, these technologies are costly, not easily multiplexed, and require advanced imaging technologies. While the current clinical applications of protease-responsive technologies in oncologic settings are still limited, emerging technologies and protease sensors are poised to enable comprehensive exploration of the tumor proteolytic landscape as a diagnostic and therapeutic frontier. This review aims to give an overview of the most relevant classes of proteases as indicators for tumor diagnosis, current approaches to detect and monitor their activity in vivo, and associated therapeutic applications. 相似文献
8.
Thomas R. Savage Fernando Almeida-Trasvina Ehecatl A. del-Rio Chanona Robin Smith Dondga Zhang 《American Institute of Chemical Engineers》2021,67(11):e17358
With liquefied natural gas becoming increasingly prevalent as a flexible source of energy, the design and optimization of industrial refrigeration cycles becomes even more important. In this article, we propose an integrated surrogate modeling and optimization framework to model and optimize the complex CryoMan Cascade refrigeration cycle. Dimensionality reduction techniques are used to reduce the large number of process decision variables which are subsequently supplied to an array of Gaussian processes, modeling both the process objective as well as feasibility constraints. Through iterative resampling of the rigorous model, this data-driven surrogate is continually refined and subsequently optimized. This approach was not only able to improve on the results of directly optimizing the process flow sheet but also located the set of optimal operating conditions in only 2 h as opposed to the original 3 weeks, facilitating its use in the operational optimization and enhanced process design of large-scale industrial chemical systems. 相似文献
9.
Jiatong Zhu Xuanyu Meng Ping Zhang Zhuolun Li Jie Xu Michael J. Reece Feng Gao 《Journal of the European Ceramic Society》2021,41(4):2861-2869
A series of rare earth zirconates (RE2Zr2O7) high-entropy ceramics with single- and dual-phase structure were prepared. Compared with La2Zr2O7 and Yb2Zr2O7, the smaller “rattling” ions (Yb3+, Er3+, Y3+) have been incorporated into pyrochlore lattice in (La0.2Nd0.2Y0.2Er0.2Yb0.2)2Zr2O7 (LNYEY) while larger ions (La3+, Nd3+, Sm3+, Eu3+) incorporated into fluorite lattice in (La0.2Nd0.2Sm0.2Gd0.2Yb0.2)2Zr2O7 (LNSGY). Due to high-entropy lattice distortion and resonant scattering derived from smaller ions Yb3+, Er3+, and Y3+, LNYEY shows a lower glass-like thermal conductivity (1.62-1.59 W m-1 K-1, 100-600℃) than LNSGY (1.74-1.75 W m-1 K-1, 100-600℃). Moreover, LNYEY and LNSGY exhibit enhanced Vickers’ hardness (LNYEY, Hv = 11.47 ± 0.41 GPa; LNSGY, Hv = 10.96 ± 0.26 GPa) and thermal expansion coefficients (LNYEY, 10.45 × 10-6 K-1, 1000℃; LNSGY, 11.02 × 10-6 K-1, 1000℃). These results indicate that dual-phase rare-earth-zirconate high-entropy ceramics could be desirable for thermal barrier coatings. 相似文献
10.
Felix Kexel Alexandra von Kameke Janina Tenhaus Marko Hoffmann Michael Schlüter 《化学,工程师,技术》2021,93(5):830-837
A consecutive competitive gas-liquid reaction is investigated using a Taylor bubble setup regarding the influence of fluid mixing in the bubble wake on yield and selectivity. The concentration fields behind a Taylor bubble are visualized and measured quantitatively with a novel time-resolved absorption imaging technique based on Beer Lamberts law and an integral selectivity is derived. In addition, the calculation of the local selectivity, often used in numerical approaches, is discussed and the existing experimental limits for its derivation are pointed out. Finally, an increase in selectivity of a competitive consecutive reaction for enhanced mixing is experimentally confirmed. 相似文献