Stable 3D Deep Convolutional Autoencoder Method for Ultrasonic Testing of Defects in Polymer Composites.

Ultrasonic testing is widely used for defect detection in polymer composites owing to advantages such as fast processing speed, simple operation, high reliability, and real-time monitoring. However, defect information in ultrasound images is not easily detectable because of the influence of ultrasound echoes and noise. In this study, a stable three-dimensional deep convolutional autoencoder (3D-DCA) was developed to identify defects in polymer composites. Through 3D convolutional operations, it can synchronously learn the spatiotemporal properties of the data volume. Subsequently, the depth receptive field (RF) of the hidden layer in the autoencoder maps the defect information to the original depth location, thereby mitigating the effects of the defect surface and bottom echoes. In addition, a dual-layer encoder was designed to improve the hidden layer visualization results. Consequently, the size, shape, and depth of the defects can be accurately determined. The feasibility of the method was demonstrated through its application to defect detection in carbon-fiber-reinforced polymers.

Data-driven calibration of decoupling matrix for MIMO precision motion stages.

Decoupling control is a commonly employed technique for achieving high precision in multiple-input multiple-output (MIMO) motion control systems. A static decoupling matrix, which can be determined using geometric construction, is widely used due to its practicality and simplicity. However, inaccurate geometric parameters will lead to a coarse decoupling matrix, and result in interactions among the system axes and performance deterioration. To tackle this challenge, various attempts have been undertaken to calibrate the decoupling matrix. Data-driven on-line approaches have gained considerable attention for their ability to calibrate the decoupling matrix without interrupting the normal operation of the system. This paper presents a data-driven approach to calibrate the decoupling matrix for MIMO and linear time invariant (LTI) systems. Through some reasonable assumptions, a calibrated static decoupling matrix can be derived to improve the performance of the system. Moreover, considering the inevitable presence of measurement noise, the consistency of the proposed method has been analyzed. As a result, the instrument variable is introduced in the improved method to eliminate the impact of the measurement noise. Finally, the effectiveness and practicality of the proposed method are demonstrated through both numerical simulations and experiments carried out on an ultraprecision wafer stage.

Increased Deep Trap Density in Interfacial Engineered Nanocomposite Revealed by Sequential Kelvin Probe Force Microscopy for High Dielectric Energy Storage.

Nanocomposites combining inorganic nanoparticles with high dielectric constant and polymers with high breakdown strength are promising for the high energy density storage of electricity, and carrier traps can significantly affect the dielectric breakdown process. Nevertheless, there still lacks direct experimental evidence on how nanoparticles affect the trap characteristics of nanocomposites, especially in a spatially resolved manner. Here, a technique is developed to image the trap distribution based on sequential Kelvin probe force microscopy (KPFM) in combination with the isothermal surface potential decay (ISPD) technique, wherein both shallow and deep trap densities and the corresponding energy levels can be mapped with nanoscale resolution. The technique is first validated using the widely-used commercial biaxially oriented polypropylene, yielding consistent results with macroscopic ISPD. The technique is then applied to investigate polyvinylidene fluoride-based nanocomposites filled with barium titanate nanoparticles, revealing higher deep trap density around surface-modified nanoparticles, which correlates well with its increased breakdown strength. This technique thus provides a powerful spatially resolved tool for understanding the microscopic mechanism of dielectric breakdown of nanocomposites.

The antiprotozoal drug nitazoxanide improves experimental liver fibrosis in mice.

Nitazoxanide is an FDA-approved antiprotozoal drug. Our previous studies find that nitazoxanide and its metabolite tizoxanide affect AMPK, STAT3, and Smad2/3 signals which are involved in the pathogenesis of liver fibrosis, therefore, in the present study, we examined the effect of nitazoxanide on experimental liver fibrosis and elucidated the potential mechanisms. The in vivo experiment results showed that oral nitazoxanide (75, 100 mg·kg-1) significantly improved CCl4- and bile duct ligation-induced liver fibrosis in mice. Oral nitazoxanide activated the inhibited AMPK and inhibited the activated STAT3 in liver tissues from liver fibrosis mice. The in vitro experiment results showed that nitazoxanide and its metabolite tizoxanide activated AMPK and inhibited STAT3 signals in LX-2 cells (human hepatic stellate cells). Nitazoxanide and tizoxanide inhibited cell proliferation and collagen I expression and secretion of LX-2 cells. Nitazoxanide and tizoxanide inhibited transforming growth factor-ß1 (TGF-ß1)- and IL-6-induced increases of cell proliferation, collagen I expression and secretion, inhibited TGF-ß1- and IL-6-induced STAT3 and Smad2/3 activation in LX-2 cells. In mouse primary hepatic stellate cells, nitazoxanide and tizoxanide also activated AMPK, inhibited STAT3 and Smad2/3 activation, inhibited cell proliferation, collagen I expression and secretion. In conclusion, nitazoxanide inhibits liver fibrosis and the underlying mechanisms involve AMPK activation, and STAT3 and Smad2/3 inhibition.

Research on directional rock blasting based on different slotted pipe materials of the combined charge structure.

For shaped charge blasting projects in mining, civil engineering, and similar fields, it is proposed to modify the charge structure by combining slotted tubes and shaped charge liners to obtain a new type of charge structure. This aims to achieve directional rock breaking through the focused action of the shaped charge. The influence of different slotted pipe materials on the directional rock-breaking effect of concentrated energy using a new charge structure is explored through theoretical analysis combined with model test study, high-speed camera, stress-strain gauge, and other equipment. A comparison is made between slotted pipes made of aluminum, kraft paper, and PVC, with the cutting width of 2 mm. Based on the characteristics of the cracks formed after blasting, the new charge structure made of aluminum slotted pipe produces a penetrating crack that is almost consistent with the pre-cracking direction. Based on the corresponding characteristics of successively released blasting energy, the guiding and convergence effect of the new charge structure made of aluminum slotted pipe on the explosion energy is greater than that of the new charge structure made of the other two types of slotted pipe material. According to the strain data measured after blasting, the peak arrival time of the strain peak in the direction of the slotted pipe on one side of the shaped hood is shorter than that in the other two directions, and the peak strain is greater than that in the other two directions while having a better energy gathering effect. Based on the findings, the new charge structure with directional energy concentration has a damage reduction effect. Furthermore, the material of aluminum slotted pipe is found to be better than PVC slotted pipe, whereas the material of PVC slotted pipe is better than kraft paper slotted pipe in achieving directional rock breaking.

Ternary ReS2(1-x)Se2xalloys of different composition for Q-switched and mode-locked all-fiber laser.

This paper systematically studied the composition-controlled nonlinear optical properties and pulse modulation of ternary ReS2(1-x)Se2xalloys for the first time. The compositionally modulated characteristics of ReS2(1-x)Se2xon the band gap were simulated based on the first principles. We investigated the effect of the band gap on the saturable absorption properties. In addition, we demonstrated the modulation characteristics of different components ReS2(1-x)Se2xon 1.5µm Q-switched pulse performance. The Q-switched threshold, repetition rate, and pulse duration increase as the S(sulfur)-element composition rise. And pulse energy also was affected by the S(sulfur)-element composition. The ReS0.8Se1.2SA was selected to realize a conventional soliton with high energy in the all-fiber mode-locked laser. The pulse was centered at 1562.9 nm with a pulse duration of 2.26 ps, a repetition rate of 3.88 MHz, and maximum pulse energy of 1.95 nJ. This work suggests that ReS2(1-x)Se2xhas great potential in laser technology and nonlinear optics, and widely extends the material applications in ultrafast photonics.

Effect of Bionic Crab Shell Attitude Parameters on Lift and Drag in a Flow Field.

Underwater bionic-legged robots encounter significant challenges in attitude, velocity, and positional control due to lift and drag in water current environments, making it difficult to balance operational efficiency with motion stability. This study delves into the hydrodynamic properties of a bionic crab robot's shell, drawing inspiration from the sea crab's motion postures. It further refines the robot's underwater locomotion strategy based on these insights. Initially, the research involved collecting attitude data from crabs during underwater movement through biological observation. Subsequently, hydrodynamic simulations and experimental validations of the bionic shell were conducted, examining the impact of attitude parameters on hydrodynamic performance. The findings reveal that the transverse angle predominantly influences lift and drag. Experiments in a test pool with a crab-like robot, altering transverse angles, demonstrated that increased transverse angles enhance the robot's underwater walking efficiency, stability, and overall performance.

Bacteriophage therapy for drug-resistant Staphylococcus aureus infections.

Drug-resistant Staphylococcus aureus stands as a prominent pathogen in nosocomial and community-acquired infections, capable of inciting various infections at different sites in patients. This includes Staphylococcus aureus bacteremia (SaB), which exhibits a severe infection frequently associated with significant mortality rate of approximately 25%. In the absence of better alternative therapies, antibiotics is still the main approach for treating infections. However, excessive use of antibiotics has, in turn, led to an increase in antimicrobial resistance. Hence, it is imperative that new strategies are developed to control drug-resistant S. aureus infections. Bacteriophages are viruses with the ability to infect bacteria. Bacteriophages, were used to treat bacterial infections before the advent of antibiotics, but were subsequently replaced by antibiotics due to limited theoretical understanding and inefficient preparation processes at the time. Recently, phages have attracted the attention of many researchers again because of the serious problem of antibiotic resistance. This article provides a comprehensive overview of phage biology, animal models, diverse clinical case treatments, and clinical trials in the context of drug-resistant S. aureus phage therapy. It also assesses the strengths and limitations of phage therapy and outlines the future prospects and research directions. This review is expected to offer valuable insights for researchers engaged in phage-based treatments for drug-resistant S. aureus infections.

Integrated evaluation of biomechanical and biological properties of the biomimetic structural bone scaffold: Biomechanics, simulation analysis, and osteogenesis.

A porous structure is essential for bone implants because it increases the bone ingrowth space and improves mechanical and biological properties. The biomimetically designed porous Voronoi scaffold can reconstruct the structure and function of cancellous bone; however, its comprehensive properties need to be investigated further. In this study, algorithms based on scaling factors were used to design the Voronoi scaffolds. Classic approaches, such as computer-aided design and the implicit surface method, have been used to design Diamond, Gyroid, and I-WP scaffolds as controls. All scaffolds were prepared by selective laser melting of titanium alloys and three-dimensional printing. Mechanical tests, finite element analysis, and in vitro and in vivo experiments were performed to investigate the biomechanical, cytologic, and osteogenic performance of the scaffolds, while computational fluid dynamics simulations were used to explore the underlying mechanisms. Diamond scaffolds have a better loading capacity, and the mechanical behaviors and fluid flow of Voronoi scaffolds are similar to those of the human trabecular bone. Cells showed more proliferation and distribution on the Diamond and Voronoi scaffolds and exhibited evident differentiation on Gyroid and Voronoi scaffolds. Bone formation was apparent on the inner part of the Gyroid, the outer part of the I-WP, and the entire Diamond and Voronoi scaffolds. The hydrodynamic properties and stimulus response of cells influenced by the porous structure account for the varied biological performance of the scaffolds. The Voronoi scaffolds with bionic mechanical behavior and an appropriate hydrodynamic response exhibit evident cell growth and osteogenesis, making them preferable for porous structural bone implants.

Integrated omics landscape of hepatocellular carcinoma suggests proteomic subtypes for precision therapy.

Patients with hepatocellular carcinoma (HCC) at the same clinical stage can have extremely different prognoses, and molecular subtyping provides an opportunity for individualized precision treatment. In this study, genomic, transcriptomic, proteomic, and phosphoproteomic profiling of primary tumor tissues and paired para-tumor tissues from HCC patients (N = 160) are integrated. Proteomic profiling identifies three HCC subtypes with different clinical prognosis, which are validated in three publicly available external validation sets. A simplified panel of nine proteins associated with metabolic reprogramming is further identified as a potential subtype-specific biomarker for clinical application. Multi-omics analysis further reveals that three proteomic subtypes have significant differences in genetic alterations, microenvironment dysregulation, kinase-substrate regulatory networks, and therapeutic responses. Patient-derived cell-based drug tests (N = 26) show personalized responses for sorafenib in three proteomic subtypes, which can be predicted by a machine-learning response prediction model. Overall, this study provides a valuable resource for better understanding of HCC subtypes for precision clinical therapy.

Designing Benzodithiophene-Based Small Molecule Donors for Organic Solar Cells by Regulation of Halogenation Effects.

The donors are key components of organic solar cells (OSCs) and play crucial roles in their photovoltaic performance. Herein, we designed two new donors (BTR-γ-Cl and BTR-γ-F) by finely optimizing small molecule donors (BTR-Cl and BTR-F) with a high performance. The optoelectronic properties of the four donors and their interfacial properties with the well-known acceptor Y6 were studied by density functional theory and time-dependent density functional theory. Our calculations show that the studied four donors have large hole mobility and strong interactions with Y6, where the BTR-γ-Cl/Y6 has the largest binding energy. Importantly, the proportion of charge transfer (CT) states increases at the BTR-γ-Cl/Y6 (50%) and BTR-γ-F/Y6 (45%) interfaces. The newly designed donors are more likely to achieve CT states through intermolecular electric field (IEF) and hot exciton mechanisms than the parent molecules; meanwhile, donors containing Cl atoms are more inclined to produce CT states through the direct excitation mechanism than those containing F atoms. Our results not only provided two promising donors but also shed light on the halogenation effects on donors in OSCs, which might be important to design efficient photovoltaic materials.

Astragaloside IV protects against lung injury and pulmonary fibrosis in COPD by targeting GTP-GDP domain of RAS and downregulating the RAS/RAF/FoxO signaling pathway.

BACKGROUND: Pulmonary fibrosis is a chronic progressive interstitial lung disease characterized by the replacement of lung parenchyma with fibrous scar tissue, usually as the final stage of lung injury like COPD. Astragaloside IV (AST), a bioactive compound found in the Astragalus membranaceus (Fisch.) used in traditional Chinese medicine, has been shown to improve pulmonary function and exhibit anti-pulmonary fibrosis effects. However, the exact molecular mechanisms through which it combats pulmonary fibrosis, especially in COPD, remain unclear. PURPOSE: This study aimed to identify the potential therapeutic target and molecular mechanisms for AST in improving lung injury especially treating COPD type pulmonary fibrosis both in vivo and in vitro. METHODS: Multi lung injury models were established in mice using lipopolysaccharide (LPS), cigarette smoke (CS), or LPS plus CS to simulate the processes of pulmonary fibrosis in COPD. The effect of AST on lung function protection was evaluated, and proteomic and metabolomic analysis were applied to identify the signaling pathway affected by AST and to find potential targets of AST. The interaction between AST and wild-type and mutant RAS proteins was studied. The RAS/RAF/FoxO signaling pathway was stimulated in BEAS-2B cells and in mice lung tissues by LPS plus CS to investigate the anti-pulmonary fibrosis mechanism of AST analyzed by western blotting. The regulatory effects of AST on the RAS/RAF/FoxO pathway dependent on RAS were further confirmed using RAS siRNA. RESULTS: RAS was predicted and identified as the target protein of AST in anti-pulmonary fibrosis in COPD and improving lung function. The administration of AST was observed to impede the conversion of fibroblasts into myofibroblasts, reduce the manifestation of inflammatory factors and extracellular matrix, and hinder the activation of epithelial mesenchymal transition (EMT). Furthermore, AST significantly suppressed the RAS/RAF/FoxO signaling pathway in both in vitro and in vivo settings. CONCLUSION: AST exhibited lung function protection and anti-pulmonary fibrosis effect by inhibiting the GTP-GDP domain of RAS, which downregulated the RAS/RAF/FoxO signaling pathway. This study revealed AST as a natural candidate molecule for the protection of pulmonary fibrosis in COPD.

Generative Deep Learning-Based Thermographic Inspection of Artwork.

Infrared thermography is a widely utilized nondestructive testing technique in the field of artwork inspection. However, raw thermograms often suffer from problems, such as limited quantity and high background noise, due to limitations inherent in the acquisition equipment and experimental environment. To overcome these challenges, there is a growing interest in developing thermographic data enhancement methods. In this study, a defect inspection method for artwork based on principal component analysis is proposed, incorporating two distinct deep learning approaches for thermographic data enhancement: spectral normalized generative adversarial network (SNGAN) and convolutional autoencoder (CAE). The SNGAN strategy focuses on augmenting the thermal images, while the CAE strategy emphasizes enhancing their quality. Subsequently, principal component thermography (PCT) is employed to analyze the processed data and improve the detectability of defects. Comparing the results to using PCT alone, the integration of the SNGAN strategy led to a 1.08% enhancement in the signal-to-noise ratio, while the utilization of the CAE strategy resulted in an 8.73% improvement.

Amorphous RuO2 Catalyst for Medium Size Carboxylic Acid to Alkane Dimer Selective Kolbe Electrolysis in an Aqueous Environment.

The catalytic transformation of biomass-derived volatile carboxylic acids in an aqueous environment is crucial to developing a sustainable biorefinery. To date, Kolbe electrolysis remains arguably the most effective means to convert energy-diluted aliphatic carboxylic acids (carboxylate) to alkane for biofuel production. This paper reports the use of a structurally disordered amorphous RuO2 (a-RuO2 ) that is synthesized facilely in a hydrothermal method. The a-RuO2 is highly effective towards electrocatalytic oxidative decarboxylation of hexanoic acid and is able to produce the Kolbe product, decane, with a yield 5.4 times greater than that of commercial RuO2 . A systematic study of the reaction temperature, current intensity, and electrolyte concentration reveals the enhanced Kolbe product yield is attributable to the more efficient oxidation of the carboxylate anions for the alkane dimer formation. Our work showcases a new design idea for establishing an efficient electrocatalysts for decarboxylation coupling reaction, providing a new electrocatalyst candidate for Kolbe electrolysis.

A Silicon Sub-Bandgap Near-Infrared Photodetector with High Detectivity Based on Textured Si/Au Nanoparticle Schottky Junctions Covered with Graphene Film.

We present a straightforward approach to develop a high-detectivity silicon (Si) sub-bandgap near-infrared (NIR) photodetector (PD) based on textured Si/Au nanoparticle (NP) Schottky junctions coated with graphene film. This is a photovoltaic-type PD that operates at 0 V bias. The texturing of Si is to trap light for NIR absorption enhancement, and Schottky junctions facilitate sub-bandgap NIR absorption and internal photoemission. Both Au NPs and the texturing of Si were made in self-organized processes. Graphene offers additional pathways for hot electron transport and to increase photocurrent. Under 1319 nm illumination at room temperature, a responsivity of 3.9 mA/W and detectivity of 7.2 × 1010 cm × (Hz)1/2/W were obtained. Additionally, at -60 °C, the detectivity increased to 1.5 × 1011 cm × (Hz)1/2/W, with the dark current density reduced and responsivity unchanged. The result of this work demonstrates a facile method to create high-performance Si sub-bandgap NIR PDs for promising applications at ambient temperatures.

Ginsenoside CK targeting KEAP1-DGR/Kelch domain disrupts the binding between KEAP1 and NRF2-DLG motif to ameliorate oxidative stress damage.

BACKGROUND: Panax ginseng and Panax notoginseng as traditional Chinese medicines, are widely used in the treatment of qi deficiency, viral or bacterial infection, inflammation and cancer. Ginsenoside CK, an active metabolite of protopanoxadiol among the ginseng saponins, has been shown in previous studies to improve the organism's oxidative balance by regulating the KEAP1-NRF2/ARE pathway, thus slowing the progression of diseases. However, the specific targets and mechanisms of CK in improving oxidative stress remain unclear. PURPOSE: The aim of this study was to determine the potential therapeutic targets and molecular mechanisms of CK in improving oxidative stress injury both in vitro and in vivo. METHODS: LPS was used to induce oxidative damage in RAW 264.7 cells to evaluate the regulatory effects of CK on the KEAP1-NRF2/ARE pathway. Drug affinity responsive target stability technology (DARTS) combined with proteomics was employed to identify CK's potential target proteins. CK functional probe were designed to analyze the target protein using click chemistry. Furthermore, small molecule and protein interaction technologies were used to verify the mechanism, and computer dynamic simulation technology was used to analyze the interaction sites between CK and the target protein. The pharmacological effects and mechanism of CK in improving oxidative damage were verified in vivo by LPS-induced acute injury in mice and physical mechanical injury in rat soft tissues. RESULTS: KEAP1 was identified as the target protein that CK regulates to improve oxidative damage through the KEAP1-NRF2/ARE pathway. CK competitively binds to the DGR/Kelch domain of KEAP1, disrupting the binding between DLG peptide in NRF2 and KEAP1, thereby inhibiting the occurrence of oxidative damage induced by LPS or physical mechanical stress. CONCLUSIONS: CK functions as a natural KEAP1-NRF2 inhibitor, disrupting the binding between KEAP1 and NRF2-DLG motifs by targeting the DGR/Kelch domain of KEAP1, activating the antioxidant transcriptional program of NRF2, and reducing oxidative stress damage.

Predictive model for growth of Pseudomonas spp. on fresh duck breast as a function of temperature.

This study was performed to develop a predictive growth model of Pseudomonas spp. to ensure the safety of fresh duck breast. Sterile fresh duck breasts were inoculated with Pseudomonas spp. and stored at 4°C, 10°C, 15°C, 20°C, 25°C, and 30°C to measure the microbial change. The Baranyi primary model was used to simulate the growth changes of Pseudomonas spp. at different temperatures. The square root type model and hyperbolic function as secondary models were used to model the effect of temperature on the maximum specific growth rate and lag phase duration. The results showed that the primary models fitted the growth data well (all R2 > 0.900 and RMSE were close to 0). In validation study of secondary model, R2 were 0.987 and 0.925, RMSE were 0.017 and 1.825, respectively, indicating that the parameters of primary models were accurately predicted by secondary models. The validation experiments at tested temperatures proved that the changes of Pseudomonas spp. could be predicted accurately by the developed models combining primary and secondary models both at constant and variable temperatures. The model could be applied to predict the growth of Pseudomonas spp. in logistics for avoiding microbial spoilage on fresh duck breast.

Nanomaterial-based magnetic surface molecularly imprinted polymers for specific extraction and efficient recognition of dibutyl phthalate.

A rapid and selective sorbent for the enrichment of dibutyl phthalate (DBP) from water and Chinese Baijiu samples was established using magnetic surface molecularly imprinted polymers (MSMIPs) combined with gas chromatography-mass spectrometer (GC-MS). The MSMIPs were synthesized using a magnetic nanosphere material with silica layer, increasing the polymer surface area as a carrier. Compared with the traditional methods, the addition of magnetic microspheres simplified the process of food substrate purification and significantly shortened the pre-concentration time. The MSMIPs adsorption conforms to the Freundlich isotherm model as multilayer adsorption on an inhomogeneous surface and the pseudo-second-order model. The developed MSMIPs combined with GC-MS method showed good linearity in DBP concentration range of 0.02-1.0 mg L-1 with low LOD (0.0054 mg L-1) and LOQ (0.018 mg L-1), and obtained good recoveries in real samples (95.2-97.2%) with RSD < 5.0% (n = 9), which were consistent with those from Chinese national standard method.

D-Optimal Design and Development of a Koumine-Loaded Microemulsion for Rheumatoid Arthritis Treatment: In vivo and in vitro Evaluation.

Introduction: Koumine (KME) is the most abundant active ingredient separated from Gelsemium elegans Benth and exhibits a significant therapeutic effect on rheumatoid arthritis (RA). It is a lipophilic compound with poor aqueous solubility, and there is an urgent need to develop novel dosage forms of KME and promote its clinical application for the treatment of RA. The aim of this study was to design and develop KME-loaded microemulsions (KME-MEs) for the effective management of RA. Methods: The composition of the microemulsion was selected by carrying out a solubility study and generating pseudoternary phase diagrams, and further optimized by D-Optimal design. The optimized KME-MEs was evaluated for particle size, viscosity, drug release, storage stability, cytotoxicity, cellular uptake, Caco-2 cell transport and everted gut sac investigations. In vivo fluorescence imaging and the therapeutic effects of KME and KME-MEs on collagen-induced arthritis (CIA) rats were also evaluated. Results: The optimized microemulsion contained 8% oil, 32% Smix (surfactant/cosurfactant) and 60% water and was used for in vivo and in vitro studies. The optimal KME-MEs exhibited a small globule size of 18.5 ± 0.14 nm and good stability over 3 months, and the release kinetics followed a first-order model. These KME-MEs had no toxic effect on Caco-2 cells but were efficiently internalized into the cytoplasm. Compared to KME, the KME-MEs displayed significantly increased permeability and absorption in Caco-2 cell monolayer assay and ex vivo everted gut sac experiment. As expected, the KME-MEs attenuated the progression of RA in CIA rats and were more effective than free KME with a reduced frequency of administration. Conclusion: The KME-MEs improved the solubility and therapeutic efficacy of KME by employing formulation technology. These results provide a promising vehicle for the oral delivery of KME to treat RA and have attractive potential for clinical translation.

Astragaloside IV targets PRDX6, inhibits the activation of RAC subunit in NADPH oxidase 2 for oxidative damage.

BACKGROUND: Radix Astragali Mongolici, as a traditional Chinese medicine, is widely used in the treatment of qi deficiency, viral or bacterial infection, inflammation and cancer. Astragaloside IV (AST), a key active compound in Radix Astragali Mongolici, has been shown to reduce disease progression by inhibiting oxidative stress and inflammation. However, the specific target and mechanism of action of AST in improving oxidative stress are still unclear. PURPOSE: This study aims to explore the target and mechanism of AST to improve oxidative stress, and to explain the biological process of oxidative stress. METHODS: AST functional probes were designed to capture target proteins and combined with protein spectrum to analyze target proteins. Small molecule and protein interaction technologies were used to verify the mode of action, while computer dynamics simulation technology was used to analyze the site of interaction with the target protein. The pharmacological activity of AST in improving oxidative stress was evaluated in a mouse model of acute lung injury induced by LPS. Additionally, pharmacological and serial molecular biological approaches were used to explore the underlying mechanism of action. RESULTS: AST inhibits PLA2 activity in PRDX6 by targeting the PLA2 catalytic triad pocket. This binding alters the conformation and structural stability of PRDX6 and interferes with the interaction between PRDX6 and RAC, hindering the activation of the RAC-GDI heterodimer. Inactivation of RAC prevents NOX2 maturation, attenuates superoxide anion production, and improves oxidative stress damage. CONCLUSION: The findings of this research indicate that AST impedes PLA2 activity by acting on the catalytic triad of PRDX6. This, in turn, disrupts the interaction between PRDX6 and RAC, thereby hindering the maturation of NOX2 and diminishing the oxidative stress damage.