Developing nuclear factor erythroid-2 related factor 2 (Nrf2)-dependent cytoprotectors against oxidative damage is of concern because they can effectively reduce the risk of oxidative stress-related ...diseases, such as cancer and inflammation. This work was aimed to develop more active Nrf2-dependent cytoprotectors than curcumin, a well-known dietary Nrf2 activator and cancer chemopreventive agent. Herein we designed a panel of curcumin-inspired mono-carbonyl piperidinone analogs differentiated by placing distinct electron-withdrawing and electron-donating groups on its two aromatic rings in the ortho, meta, or para position to the linker of α, β-unsaturated piperidinone. Among these, the ortho-fluorine-substituted CN–2F surfaced as a promising lead molecule, which was significantly superior to the parent curcumin in protecting HepG2 cells from oxidative damage induced by tert-butyl hydroperoxide. Mechanically, by virtue of its Michael receptor units and ortho-substituted mode, CN–2F activated Nrf2 signaling by covalently modifying Cys-151 and Cys-288 residues at Keap1, promoting phosphorylation of JNK, ERK and p38, as well as inhibiting Nrf2 degradation. This work reveals the structural determinants and the activity mechanisms of CN–2F as an Nrf2-dependent cytoprotector, and gives useful information on how to design curcumin-inspired Nrf2 activators and cytoprotectors.
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•Designing a panel of curcumin-inspired mono-carbonyl piperidinone analogs.•Clarifying on their structure-activity relationship and mechanisms as Nrf2-dependent cytoprotectors.•Michael receptor units and ortho-substituted mode allow CN–2F as a promising lead.•Giving useful information on how to design curcumin-inspired Nrf2-dependent cytoprotectors.
The main purpose of this study was to reveal the nutritional value and antioxidant activity of 34 edible flowers that grew in Yunnan Province, China, through a comprehensive assessment of their ...nutritional composition and antioxidant indices. The results showed that sample A3 of Asteraceae flowers had the highest total flavonoid content, with a value of 8.53%, and the maximum contents of vitamin C and reducing sugars were from Rosaceae sample R1 and Gentianaceae sample G3, with values of 143.80 mg/100 g and 7.82%, respectively. Samples R2 and R3 of Rosaceae were the top two flowers in terms of comprehensive nutritional quality. In addition, the antioxidant capacity of Rosaceae samples was evidently better than that of three others, in which Sample R1 had the maximum values in hydroxyl radical (
OH) scavenging and superoxide anion radical (
O
) scavenging rates, and samples R2 and R3 showed a high total antioxidant capacity and 2,2-diphenyl-1-pyridylhydrazine (DPPH) scavenging rate, respectively. Taken together, there were significant differences in the nutrient contents and antioxidant properties of these 34 flowers, and the comprehensive quality of Rosaceae samples was generally better than the other three families. This study provides references for 34 edible flowers to be used as dietary supplements and important sources of natural antioxidants.
Ignition electrodes have an immense impact on the accurate measurement of the flame propagation spherical radius. In this study, a flame-radius calculation method is designed. The method is able to ...eliminate effects due to the ignition electrodes. The adaptability and optimization effects of the proposed method are analyzed. The results show that the ratio of the angle is affected by the ignition electrodes under the Han II method. There are three obvious divisions include a high-value area, a sharp-variation area, and a mild-variation area. The ratio of the angle affected by the ignition electrodes is only applicable to the mild-variation region when the flame presents respective convex and concave distributions. For these distributions, the increment rate of the mean radius is 0.4-0.85% and 0.42-3.19%. The reduced rate of the standard deviation of the radius extraction value is 11.91-22.1% and 5.13-17.99%, and the reduced rate of the radius extraction value range is 20.32-39.51% and 0.32-8.09%.
In this study, a method was developed to calculate the radius of a spherical expanding flame, with the goal of mitigating the effects of the ignition electrode. This approach allows for a swift ...determination of the ignition electrode's influence on the spherical expanding flame. It also facilitates accurate computation of the flame radius and offers a systematic means to validate the derived laminar burning velocity. Using this method as a foundation, an evaluation system was established to examine factors that could impact the method's results. Findings suggest that the laminar burning velocity determined by this method aligns more closely with numerical simulations and experimental data from referenced studies. For spherical expanding flames with convex and concave contours near the ignition electrode, the mean flame radius decreases by 0.57% to 1.22% and increases by 1.37% to 2.95%, respectively.
•Constant volume combustion vessel and Schlieren photography system were used.•A calculation method was proposed to mitigate the effects of the ignition electrode.•The optimization of this calculation method was verified.•An evaluation system was established to examine the impact factors.
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•Ceritinib analogs (8–42) were identified as ALK/ROS1 dual inhibitors.•39 displayed remarkable antitumor effects on ALK & ROS1-addicted cancer cells.•39 exerted significant potency ...against ALK and ROS1 verified by molecular docking.•39 displayed impressive mutant-combating effects in cellular & enzymatic assays.•39 induced apoptosis of H2228 cell in a dose-dependent manner.
The pyrimidine-2,4-diamine analogs exerted excellent activities in down-regulation of ALK phosphorylation. However, the prevalent drug-resistant site-mutation has gradually prevented the agents from being widely used. Herein, we conducted an exploration of high affinity moiety that bound to the solvent-front region (G1202R located) within the ATP binding site of ALK leading to the synthesis of thirty-five pyrimidine-2,4-diamine derivatives. Among these compounds, urea group was extensively derivatized which finally resulted in the identification of the ‘semi-free urea’ compound 39. All compounds were assayed cytotoxicity and enzymatic activities and 39 turned out to be the most potent one with IC50 values of 2.1, 0.91, 4.3 and 0.73 nM towards ALKwt, ALKL1196M, ALKG1202R and ROS1, respectively. The performances of 39 on ALK- & ROS1-dependent cell lines were in good accordance with enzymatic activities with IC50 values below 0.06 µM. Besides, 39 induced cell apoptosis in a dose-dependent manner in H2228 cells. Finally, the binding models of 39 with ALKwt, ROS1, ALKL1196M and ALKG1202R were ideally established which further clearly elucidated their mode of action within the active site.
•K-Ce catalysts promote the low temperature combustion of soot by enhancing contact with soot particles and increasing oxygen vacancies.•Catalytic activity is optimal when the molar ratio of K/(K+Ce) ...is 0.2 and soot/KC-0.2 mixture weight ratios is feasible below 1:10.•K-Ce catalysts and K-Ce based mixed catalysts have good stability at temperatures lower than 600 °C.•Mixed catalysts with commercial catalysts participation are synthetized to further study the catalytic effect of KC-0.2 based mixed catalyst on soot combustion.
A series of K-Ce catalysts with different K/(K+Ce) molar ratios are successfully prepared by hydrothermal method, to optimize catalyst diesel particlate filter (CDPF) regeneration efficiency of soot elimination. The K-Ce catalyst is an excellent promoter for soot combustion by thermogravimetric analysis (TGA), and the KC-0.2 catalyst has the best catalytic activity because proper K ions lead to more oxygen vacancies and improve contact efficiency with soot. This result corresponds well to characterization analysis, such as XRD, SEM and XPS. In a 10%O2/90%N2 atmosphere, the KC-0.2 has the highest average mass loss rate (Wmean), maximum mass loss rate (Wmax) and combustion stability index (Rw). The weight ratios of the soot/KC-0.2 mixture are less than 1:10, making catalytic oxidation easier for the soot. Thermal aging in static air at 600 °C is used to investigate the catalytic stability of KC-0.2, and the TGA results show that KC-0.2 has good stability at temperatures lower than 600 °C. Compare to KC-0.2, the KC-0.2 based mixed catalyst with ZrO2 participation is further prepared by mechanical method and has better catalytic activity because the presence of Zr enhances redox surface sites of catalyst. This facilitates the exploration of novel catalysts through combinatorial catalysis.
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This paper studies the effects of ash species and ash aging deposition on the physical and chemical properties of KC catalysts. By thermogravimetric analysis (TGA), the pure KC catalyst has good ...stability and catalytic activity at 600 °C. In the loosely contacting soot particles (PU)/ash/KC mixtures, the negative effect of ash on KC catalytic soot oxidation is relatively weak. The addition of ash makes the active site areas between PU and KC catalyst lose contact without changing the physicochemical properties of the catalyst. By contrast, the ash aging deposition on KC at 400 °C has an obviously negative effect on the soot combustion catalyzed by KC, because ash aging deposition leads to enormous changes in the chemical properties and catalytic activity of KC. This finding is consistent with characterization analyses such as XRD, SEM, XPS and Raman. Ash aging deposition destroys the KC structure and reduces the activity of KC to catalyze soot oxidation, and CaSO4 has the greatest effect on the oxidation activity. Consequently, ash aging deposition causes structural property damage of as-prepared catalysts, leading to the failure of CDPF catalytic layer. This study provides a new idea for the selection and optimization strategy of catalysts in CDPF.
•In loosely contact PU/ash/KC mixtures, the negative effect of ash on KC catalytic soot oxidation is relatively weak.•At 400 °C, ash aging deposition will lead to destruction of physicochemical properties of KC, and CaSO4 has the greatest negative effect on the catalytic activity of catalyst.•The ash aging deposition can destroy the catalytic activity of KC to the greatest extent within 20 h at 400 °C aging temperature.
Background: As the first line of immune defense and the largest organ of body, skin is vulnerable to damage caused by surgery, bums, collisions and other factors. Wound healing in the skin is a long ...and complex physiological process that is influenced by a number of different factors. Proper wound care can greatly improve the speed of wound healing and reduce the generation of scars. However, traditional wound dressings (bandages, gauze, etc.) often used in clinical practice have a single function, lack of active ingredients and are limited in use. Hydrogels with three-dimensional network structure are a potential biomedical material because of their physical and chemical environment similar to extracellular matrix. In particular, hydrogel dressings with low price, good biocompatibility, degradability, antibacterial and angiogenic activity are favored by the public. Methods: Here, a carboxymethyl chitosan-based hydrogel dressing (CMCS-TA/Cu.sup.2+) reinforced by copper ion crosslinked tannic acid (TA/Cu.sup.2+) nanoparticles was developed. This study investigated the physical and chemical characteristics, cytotoxicity, and angiogenesis of TA/Cu.sup.2+ nanoparticles and CMCS-TA/Cu.sup.2+ hydrogels. Furthermore, a full-thickness skin defect wound model was employed to assess the in vivo wound healing capacity of hydrogel dressings. Results: The introduction of TA/Cu.sup.2+ nanoparticles not only could increase the mechanical properties of the hydrogel but also continuously releases copper ions to promote cell migration (the cell migration could reach 92% at 48 h) and tubule formation, remove free radicals and promote wound healing (repair rate could reach 90% at 9 days). Conclusion: Experiments have proved that CMCS-TA/Cu.sup.2+ hydrogel has good cytocompatibility, antioxidant and wound healing ability, providing an advantageous solution for skin repair. Keywords: TA/Cu.sup.2+ nanoparticles, carboxymethyl chitosan, wound dressing, antioxidant activity
BackgroundAs the first line of immune defense and the largest organ of body, skin is vulnerable to damage caused by surgery, burns, collisions and other factors. Wound healing in the skin is a long ...and complex physiological process that is influenced by a number of different factors. Proper wound care can greatly improve the speed of wound healing and reduce the generation of scars. However, traditional wound dressings (bandages, gauze, etc.) often used in clinical practice have a single function, lack of active ingredients and are limited in use. Hydrogels with three-dimensional network structure are a potential biomedical material because of their physical and chemical environment similar to extracellular matrix. In particular, hydrogel dressings with low price, good biocompatibility, degradability, antibacterial and angiogenic activity are favored by the public.MethodsHere, a carboxymethyl chitosan-based hydrogel dressing (CMCS-TA/Cu2+) reinforced by copper ion crosslinked tannic acid (TA/Cu2+) nanoparticles was developed. This study investigated the physical and chemical characteristics, cytotoxicity, and angiogenesis of TA/Cu2+ nanoparticles and CMCS-TA/Cu2+ hydrogels. Furthermore, a full-thickness skin defect wound model was employed to assess the in vivo wound healing capacity of hydrogel dressings.ResultsThe introduction of TA/Cu2+ nanoparticles not only could increase the mechanical properties of the hydrogel but also continuously releases copper ions to promote cell migration (the cell migration could reach 92% at 48 h) and tubule formation, remove free radicals and promote wound healing (repair rate could reach 90% at 9 days).ConclusionExperiments have proved that CMCS-TA/Cu2+ hydrogel has good cytocompatibility, antioxidant and wound healing ability, providing an advantageous solution for skin repair.
Huang Y, Chen Y, Cheng G, et al. Int J Nanomedicine. 2024;19:231-245. The authors have advised due to an error that occurred inadvertently at the time of figure assembly, Figure 5C on page 240 is ...incorrect. The correct Figure 5 is as follows. Figure 5 Continued. Figure 5 Results of in vitro cytocompatibility testing. (A) CCK-8 assay and (B) cell viability on hydrogels after 1, 3 and 5 days of culture. (C) Images of live/dead staining of cells following incubation on hydrogels. (D) Images taken using a confocal laser scanning microscope (CLSM) show HUVECs stained with rhodamine-coupled phalloidin (red) and DAPI (blue) after three days of growth. A one-way ANOVA was used to determine statistical significance: *p < 0.05, **p < 0.01. The authors apologise for this error.
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