Suppression of cell pyroptosis by omeprazole through PDE4-mediated autophagy in gastric epithelial cells

Helicobacter pylori is a risk factor for the development of peptic ulcers with autophagy dysfunction.Omeprazole was widely known as the first-line regimen for H.pylori-associated gastritis.Objectives:The objective of this work was to assess the role of omeprazole on cell pyroptosis and autophagy.Methods:The clinical samples were collected.Quantitative polymerase chain reaction,western blotting,enzyme linked immunosorbent assay,and immunofluorescence(IF)analysis were conducted to reveal the mechanism of omeprazole on cell pyroptosis and autophagy.Results:The results revealed that omeprazole could decrease cell pyroptosis,which was attributed to the downregulation of cleaved caspase-1 expression,resulting in the inhibition of gasdermin E and interleukin-18/1βmaturation and secretion as well as the resolution of inflammation.Mechanistically,omeprazole treatment led to drastic downregulation of mammalian target of rapamycin(mTOR)activity was observed in BGC823 cells,leading to enhanced autophagy characterized by increased LC3II expression,which further reduced cell pyroptosis.This omeprazole-mediated phenomenon was enhanced after phosphodiesterase-4(PDE4)inhibitor dipyridamole(DIP)treatment.In addition,activation of mTOR by MHY1485 could rescue the suppression of cell pyroptosis induced by omeprazole.Most importantly,IF analysis suggested that phosphorylation of mTOR and PDE4 activity and caspase-1 were enhanced in H.pylori-infected gastric mucosa.Conclusion:These findings indicate that omeprazole suppresses cell pyroptosis through PDE4-mediated autophagy in gastric epithelial cells,and DIP enhanced the omeprazole-mediated inhibition of cell pyroptosis,implying that DIP is an alternative combined therapy strategy in improving the treatment of patients with H.pylori infection.

Enhanced stability of Fe-modified CuO-ZnO-ZrO_(2)-Al_(2)O_(3)/HZSM-5 bifunctional catalysts for dimethyl ether synthesis from CO_(2)hydrogenation

A series of iron(Fe)modified CuO-ZnO-ZrO_(2)-Al_(2)O_(3)(CZZA)catalysts,with various Fe loadings,were prepared using a co-precipitation method.A bifunctional catalyst,consisting of Fe-modified CZZA and HZSM-5,was studied for dimethyl ether(DME)synthesis via CO_(2)hydrogenation.The effects of Fe loading,reaction temperature,reaction pressure,space velocity,and concentrations of precursor for the synthesis of the Fe-modified CZZA catalyst on the catalytic activity of DME synthesis were investigated.Long-term stability tests showed that Fe modification of the CZZA catalyst improved the catalyst stability for DME synthesis via CO_(2)hydrogenation.The activity loss,in terms of DME yield,was significantly reduced from 4.2%to 1.4%in a 100 h run of reaction,when the Fe loading amount was 0.5(molar ratio of Fe to Cu).An analysis of hydrogen temperature programmed reduction revealed that the introduction of Fe improved the reducibility of the catalysts,due to assisted adsorption of H2 on iron oxide.The good stability of Femodified CZZA catalysts in the DME formation was most likely attributed to oxygen spillover that was introduced by the addition of iron oxide.This could have inhibited the oxidation of the Cu surface and enhanced the thermal stability of copper during long-term reactions.

Deep simulated annealing for the discovery of novel dental anesthetics with local anesthesia and anti-inflammatory properties

Multifunctional therapeutics have emerged as a solution to the constraints imposed by drugs with singular or insufficient therapeutic effects.The primary challenge is to integrate diverse pharmacophores within a single-molecule framework.To address this,we introduced DeepSA,a novel edit-based generative framework that utilizes deep simulated annealing for the modification of articaine,a wellknown local anesthetic.DeepSA integrates deep neural networks into metaheuristics,effectively constraining molecular space during compound generation.This framework employs a sophisticated objective function that accounts for scaffold preservation,anti-inflammatory properties,and covalent constraints.Through a sequence of local editing to navigate the molecular space,DeepSA successfully identified AT-17,a derivative exhibiting potent analgesic properties and significant anti-inflammatory activity in various animal models.Mechanistic insights into AT-17 revealed its dual mode of action:selective inhibition of NaV1.7 and 1.8 channels,contributing to its prolonged local anesthetic effects,and suppression of inflammatory mediators via modulation of the NLRP3 inflammasome pathway.These findings not only highlight the efficacy of AT-17 as a multifunctional drug candidate but also highlight the potential of DeepSA in facilitating AI-enhanced drug discovery,particularly within stringent chemical constraints.

Pd-modified CuO-ZnO-Al_(2)O_(3)catalysts via mixed-phases-containing precursor for methanol synthesis from CO_(2)hydrogenation under mild conditions

A series of palladium-modified(Pd-modified)CuO-ZnO-Al_(2)O_(3)(CZA)catalysts with various Pd loadings(0.3 wt%to 2.4 wt%)were prepared using the wetness impregnation method,on two CZA supports with different structures that are CZA-aged precursor composed of a mixture of zincian-malachite and hydrotalcite-like phases(CZA-zH),and CuO-ZnO-Al_(2)O_(3)metal oxide nanoparticles(CZA-MO).Enhancement on catalytic activity can be observed on both Pd-modified CZA catalysts in a temperature range of 180-240℃for methanol synthesis via CO_(2)hydrogenation.Pd/CZA-zH catalysts exhibited a more efficient and stable production of methanol at a relatively low reaction temperature of 180℃for 100 hrs of reaction.The improvement of activity is mainly ascribed to a higher surface area and abundant oxygen-containing functional groups(e.g.,-OH)of CZA-zH support,which is beneficial for better adsorption and distribution of Pd promoter.Hydrogen temperature programmed reduction and X-ray photoelectron spectroscopy results demonstrated a better interaction between Pd and Cu on Pd/CZA-zH catalysts via enhanced reducibility of CuO,and peak shift of Cu to a lower binding energy.The difference in the efficient utilization of hydrogen spillover effect of Pd promoter over two CZA supports resulted in the different performances for methanol synthesis under mild reaction co℃nditions.

Recent advancements and perspectives on processable natural biopolymers:Cellulose,chitosan,eggshell membrane,and silkfibroin

With the rapid development of the global economy and the continuous consumption of fossil resources,sustainable and biodegradable natural biomass has garnered extensive attention as a promising substitute for synthetic polymers.Due to their hierarchical and nanoscale structures,natural biopolymers exhibit remarkable mechanical properties,along with excellent innate biocompatibility and biodegradability,demonstrating significant potential in various application scenarios.Among these biopolymers,proteins and polysaccharides are the most commonly studied due to their low cost,abundance,and ease of use.However,the direct processing/conversion of proteins and polysaccharides into theirfinal products has been a long-standing challenge due to their natural morphology and compositions.In this review,we emphasize the importance of processing natural biopolymers into high-value-added products through sustainable and cost-effective methods.We begin with the extraction of four types of natural biopolymers:cellulose,chitosan,eggshell membrane,and silkfibroin.The processing and postfunctionalization strategies for these natural biopolymers are then highlighted.Alongside their unique structures,the versatile potential applications of these processable natural biopolymers in biomedical engineering,biosensors,environmental engineering,and energy applications are illustrated.Finally,we provide a summary and future outlook on processable natural biopolymers,underscoring the significance of converting natural biopolymers into valuable biomaterial platforms.

Effects of mixing methods of bifunctional catalysts on catalyst stability of DME synthesis via CO_(2)hydrogenation

The effects of three different mixing methods of CuO/ZnO/Al_(2)O_(3)(CZA)and HZSM-5 bifunctional catalyst on the stability for dimethyl ether(DME)synthesis from carbon dioxide(CO_(2))hydrogenation were investigated.When the bifunctional catalyst was prepared by method A(mixing powder without pelletization),there was no significant change in DME production and catalyst stability when the HZSM-5 loading was varied between 0.1 g and 0.5 g with a fixed CZA loading of 0.5 g,.When the bifunctional catalysts were prepared by method B(pressed into pellets of CZA and pellets of HZSM-5 and then mixed)and method C(mixed CZA and HZSM-5 powders,then pressed into pellets),the mixing methods did not initially impact CO_(2)conversion and had a minor effect on DME yield.However,long-term tests(100 h)indicated that the mixing method had a significant influence on the catalyst stability.Method B showed the best stability and the extent of catalyst deactivation followed the sequence of method B<method A<method C.Characterizations of spent catalysts indicated that method B could reduce the extent of copper(Cu)oxidation,which due to the relatively low surface contact between Cu active sites and HZSM-5.Large amounts of water generated in CO_(2)hydrogenation to synthesize DME and intimate contact between CZA and HZSM-5 catalyst could induce severe oxidation of Cu and metal ions migration from hydrogenation catalyst to HZSM-5,which can result in the number reduction of acidic sites.