Integrating UPLC-QTOF-MS/MS and UPLC-DAD to evaluate the influence of sulfur-fumigated Paeoniae Radix Alba on the overall quality of three Si-Wu-Tang formulations.

INTRODUCTION: Sulfur-fumigation of Paeoniae Radix Alba (PRA) could induce the chemical transformation of its bioactive component paeoniflorin into a sulfur-containing derivative paeoniflorin sulfite, and thus alter the quality, bioactivities, pharmacokinetics, and toxicities of PRA. However, how sulfur-fumigated PRA (S-PRA) affects the quality of PRA-containing complex preparations has not been intensively evaluated. OBJECTIVES: We intend to evaluate the influence of S-PRA on the overall quality of three kinds of Si-Wu-Tang (SWT) formulations, i.e., decoction (SWT-D), granule (SWT-G), and mixture (SWT-M). MATERIAL AND METHODS: An UPLC-DAD multi-components quantification method was used to compare the transfer rates of paeoniflorin sulfite and other 10 bioactive components between S-PRA-containing and NS-PRA-containing SWT formulations. An UPLC-QTOF-MS/MS-based target metabolomics approach was applied to explore the differential sulfur-containing derivatives in S-PRA-containing SWT formulations. RESULTS: The transfer rates of paeoniflorin sulfite in three S-PRA-containing SWT formulations were all higher than 100%. Moreover, S-PRA also increased the transfer rate of 5-hydroxymethylfurfural, 1,2,3,4,6-O-pentagalloylglucose, whereas decreased that of paeoniflorin, albiflorin, and ferulic acid in three SWT formulations. Six pinane monoterpene glucoside sulfites originally identified in S-PRA, were also detectable in three S-PRA-containing SWT formulations. In addition, seven phenolic acid sulfites including (3Z)-6-sulfite-ligustilide, (3E)-6-sulfite-ligustilide, 6,8-disulfite-ligustilide, ferulic acid sulfite, neochlorogenic acid sulfite, chlorogenic acid sulfite, and angelicide sulfite (or isomer) were newly identified in these three S-PRA-containing formulations. CONCLUSION: S-PRA could differentially affect the transfer rate of paeoniflorin sulfite and other bioactive components during the preparation of three SWT formulations and subsequently the overall quality thereof.

Metals/bisulfite system involved generation of 24-sulfonic-25-ene ginsenoside Rg1, a potential quality control marker for sulfur-fumigated ginseng.

Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.

Seasonal hydrological dynamics affected the diversity and assembly process of the antibiotic resistome in a canal network.

The significant threat of antibiotic resistance genes (ARGs) to aquatic environments health has been widely acknowledged. To date, several studies have focused on the distribution and diversity of ARGs in a single river while their profiles in complex river networks are largely known. Here, the spatiotemporal dynamics of ARG profiles in a canal network were examined using high-throughput quantitative PCR, and the underlying assembly processes and its main environmental influencing factors were elucidated using multiple statistical analyses. The results demonstrated significant seasonal dynamics with greater richness and relative abundance of ARGs observed during the dry season compared to the wet season. ARG profiles exhibited a pronounced distance-decay pattern in the dry season, whereas no such pattern was evident in the wet season. Null model analysis indicated that deterministic processes, in contrast to stochastic processes, had a significant impact on shaping the ARG profiles. Furthermore, it was found that Firmicutes and pH emerged as the foremost factors influencing these profiles. This study enhanced our comprehension of the variations in ARG profiles within canal networks, which may contribute to the design of efficient management approaches aimed at restraining the propagation of ARGs.

Reconstruction of a three-dimensional temperature field in flames based on ES-ResNet18.

Currently, the method of establishing the correspondence between the flame light field image and the temperature field by deep learning is widely used. Based on convolutional neural networks (CNNs), the reconstruction accuracy has been improved by increasing the depth of the network. However, as the depth of the network increases, it will lead to gradient explosion and network degradation. To further improve the reconstruction accuracy of the flame temperature field, this paper proposes an ES-ResNet18 model, in which SoftPool is used instead of MaxPool to preserve feature information more completely and efficient channel attention (ECA) is introduced in the residual block to reassign more weights to feature maps of critical channels. The reconstruction results of our method were compared with the CNN model and the original ResNet18 network. The results show that the average relative error and the maximum relative error of the temperature field reconstructed by the ES-ResNet18 model are 0.0203% and 0.1805%, respectively, which are reduced by one order of magnitude compared to the CNN model. Compared to the original ResNet18 network, they have decreased by 17.1% and 43.1%, respectively. Adding Gaussian noise to the flame light field images, when the standard deviation exceeds 0.03, the increase in reconstruction error of the ES-ResNet18 model is lower than that of ResNet18, demonstrating stronger anti-noise performance.

Engineering unactivated platelets for targeted drug delivery.

As a vital component of blood, platelets play crucial roles in hemostasis and maintaining vascular integrity, and actively participate in inflammation and immune regulation. The unique biological properties of natural platelets have enabled their utilization as drug delivery vehicles. The advancement and integration of various techniques, including biological, chemical, and physicochemical methods, have enabled the preparation of engineered platelets. Platelets can serve as drug delivery platforms combined with immunotherapy and chemokine therapy to enhance their therapeutic impact. This review focuses on the recent advancements in the application of unactivated platelets for drug delivery. The construction strategies of engineered platelets are comprehensively summarized, encompassing internal loading, surface modification, and genetic engineering techniques. Engineered platelets hold vast potential for treating cardiovascular diseases, cancers, and infectious diseases. Furthermore, the challenges and potential considerations in creating engineered platelets with natural activity are discussed.

Histone methyltransferase Suv39h1 regulates hepatic stellate cell activation and is targetable in liver fibrosis.

OBJECTIVE: Liver fibrosis is a prelude to a host of end-stage liver diseases. Hepatic stellate cells (HSCs), switching from a quiescent state to myofibroblasts, are the major source for excessive production of extracellular matrix proteins. In the present study, we investigated the role of Suv39h1, a lysine methyltransferase, in HSC-myofibroblast transition and the implication in liver fibrosis. DESIGN: HSC-specific or myofibroblast-specific Suv39h1 deletion was achieved by crossbreeding the Suv39h1 f/f mice to the Lrat-Cre mice or the Postn-CreERT2 mice. Liver fibrosis was induced by CCl4 injection or bile duct ligation. RESULTS: We report that Suv39h1 expression was universally upregulated during HSC-myofibroblast transition in different cell and animal models of liver fibrosis and in human cirrhotic liver tissues. Consistently, Suv39h1 knockdown blocked HSC-myofibroblast transition in vitro. HSC-specific or myofibroblast-specific deletion of Suv39h1 ameliorated liver fibrosis in mice. More importantly, Suv39h1 inhibition by a small-molecule compound chaetocin dampened HSC-myofibroblast transition in cell culture and mitigated liver fibrosis in mice. Mechanistically, Suv39h1 bound to the promoter of heme oxygenase 1 (HMOX1) and repressed HMOX1 transcription. HMOX1 depletion blunted the effects of Suv39h1 inhibition on HSC-myofibroblast transition in vitro and liver fibrosis in vivo. Transcriptomic analysis revealed that HMOX1 might contribute to HSC-myofibroblast transition by modulating retinol homeostasis. Finally, myofibroblast-specific HMOX1 overexpression attenuated liver fibrosis in both a preventive scheme and a therapeutic scheme. CONCLUSIONS: Our data demonstrate a previously unrecognised role for Suv39h1 in liver fibrosis and offer proof-of-concept of its targetability in the intervention of cirrhosis.

Method for Measuring the Three-Dimensional Morphology of Near-Wall Bubbles and Droplets Based on LED Digital Holography.

Digital holography, recognized for its noncontact nature and high precision in three-dimensional imaging, is effectively employed to measure the morphology of bubbles and droplets. However, in terms of near-wall bubbles and droplets, such as confined bubbles in microfluidic chips, the measurement of the interface morphology of bubbles near the glass surface has not yet been resolved due to the coherent noise resulting from glass surface reflections in microfluidic chips. Accordingly, an off-axis digital holography system was devised by using Linnik interferometry. Measuring the confined bubble interface near the wall within a microfluidic chip and droplet evaporation on solid surfaces was studied. Partially coherent LED sources and reference light modulation techniques were employed in the optical setup to mitigate the coherent noise. Dual exposure and weighted least-squares unwrapping algorithms were introduced to correct phase distortions, enhancing image quality. Imaging two confined CO2 bubbles was done near the wall in silicon oil within a porous microfluidic chip, and contact angles of 4.7 and 4.5° were measured. Additionally, the measurement of the three-dimensional morphology of vertically evaporating deionized water droplets on a glass surface was done, due to which calculation of contact angles at various orientations was possible. This work offers a feasible new method for measuring the 3D interface morphology of bubbles and droplets, particularly in microfluidic visualization, addressing current measurement gaps.

Muscle function is superior to muscle mass in predicting 90-day mortality in patients with acute-on-chronic liver failure: A prospective study.

OBJECTIVES: Low muscle mass has been found to be associated with adverse outcomes in patients with acute-on-chronic liver failure. However, data regarding the prognostic role of low muscle function are limited. Therefore, we aimed to investigate the predictive effect of low muscle function on 90-d mortality in patients with acute-on-chronic liver failure. METHODS: This prospective study consecutively enrolled acute-on-chronic liver failure patients from March 2021 to October 2022. Muscle function was assessed using the liver frailty index, and the time-dependent receiver operating characteristic curve with the highest Youden index was used to determine the optimal cutoff values of liver frailty index for diagnosing low muscle function. RESULTS: The study included 126 acute-on-chronic liver failure patients. The median liver frailty index was 3.89 (0.83), with 51 (40.5) patients classified as having low muscle function. Multivariate Cox analysis identified low muscle function (hazard ratio = 4.309; 95% CI, 1.795-10.345; P = 0.001) and number of organ failures (hazard ratio = 4.202; 95% CI, 2.040-8.656; P < 0.001) as independent risk factors for 90-d mortality. However, the multivariate analysis did not retain the significant effect of low muscle mass. Furthermore, multivariable logistic analysis revealed that age (odds ratio = 1.042; 95% CI, 1.002-1.083; P = 0.038), organ failures (odds ratio = 2.572; 95% CI, 1.331-4.968; P = 0.005), and low muscle mass (odds ratio = 6.607; 95% CI, 2.579-16.927; P < 0.001) were independent risk factors for low muscle function. CONCLUSIONS: The prognostic value of low muscle function was found superior to that of low muscle mass in patients with acute-on-chronic liver failure. Therefore, it is important to assess the muscle function and develop potential targeted treatment strategies in this population.

Bacterioplankton diversity and potential health risks in volcanic lakes: A study from Arxan Geopark, China.

Bacterioplankton play a vital role in maintaining the functions and services of lake ecosystems. Understanding the diversity and distribution patterns of bacterioplankton, particularly the presence of potential pathogenic bacterial communities, is crucial for safeguarding human health. In this study, we employed 16S rRNA gene amplicon sequencing to investigate the diversity and geographic patterns of bacterioplankton communities, as well as potential pathogens, in eight volcanic lakes located in the Arxan UNESCO Global Geopark (in the Greater Khingan Mountains of China). Our results revealed that the bacterial communities primarily comprised Bacteroidota (45.3%), Proteobacteria (33.1%), and Actinobacteria (9.0%) at the phylum level. At the genus level, prominent taxa included Flavobacterium (31.5%), Acinetobacter (11.0%), Chryseobacterium (7.9%), and CL500-29 marine group (5.6%). Among the bacterioplankton, we identified 34 pathogen genera (165 amplicon sequence variants [ASVs]), with Acinetobacter (59.8%), Rahnella (18.3%), Brevundimonas (9.6%), and Pseudomonas (5.8%) being the most dominant. Our findings demonstrated distinct biogeographic patterns in the bacterial communities at the local scale, driven by a combination of dispersal limitation and environmental factors influenced by human activities. Notably, approximately 15.3% of the bacterioplankton reads in the Arxan lakes were identified as potential pathogens, underscoring the potential risks to public health in these popular tourist destinations. This study provides the first comprehensive insight into the diversity of bacterioplankton in mountain lake ecosystems affected by high tourist activity, laying the groundwork for effective control measures against bacterial pathogens.

Antibiotics and antibiotic resistance change bacterial community compositions in marine sediments.

Emerging contaminants, including antibiotics, antibiotic-resistant bacteria (ARB), and extracellular antibiotic resistance genes (eARGs), have been detected in large numbers in the aquatic environment. The effects of emerging contaminants on bacterial communities in marine sediments are not well studied. In this study, the effects of emerging contaminants (antibiotics, ARB, and eARGs) on the variations of bacterial populations in marine sediments of the Bohai Sea, Yellow Sea, East China Sea, and South China Sea were investigated. The results showed that the abundance of the host bacterial phylum Probacteria in the marine sediments of the Bohai Sea was the lowest among the four seas after exposure to different antibiotics, ARB, and eARGs. The inputs of exogenous antibiotics and resistance genes significantly affected the community function, resulting in significant differences in community abundance at the genus level. The abundance of Halomonas, Sulfitobacter, and Alcanivorax in the four sea areas displayed noteworthy differences in response to the addition of exogenous antibiotics and eARGs. These findings contribute to a more comprehensive understanding of the intricate interplay between emerging contaminants and the dynamics of bacterial communities in natural ecosystems.

Simulating doctors' thinking logic for chest X-ray report generation via Transformer-based Semantic Query learning.

Medical report generation can be treated as a process of doctors' observing, understanding, and describing images from different perspectives. Following this process, this paper innovatively proposes a Transformer-based Semantic Query learning paradigm (TranSQ). Briefly, this paradigm is to learn an intention embedding set and make a semantic query to the visual features, generate intent-compliant sentence candidates, and form a coherent report. We apply a bipartite matching mechanism during training to realize the dynamic correspondence between the intention embeddings and the sentences to induct medical concepts into the observation intentions. Experimental results on two major radiology reporting datasets (i.e., IU X-ray and MIMIC-CXR) demonstrate that our model outperforms state-of-the-art models regarding generation effectiveness and clinical efficacy. In addition, comprehensive ablation experiments fully validate the TranSQ model's innovation and interpretation. The code is available at https://github.com/zjukongming/TranSQ.

Preparation of hydrophobic porous Au-Ag alloy nanoparticle arrays and their SERS properties.

In this study, we prepared porous Au-Ag alloy nanoparticle arrays with hydrophobic surfaces through the polystyrene colloidal crystal template combined with the chemical etching method to realize rapid SERS detection for biochemical molecules. In the preparation process, the pore size of Au-Ag alloy nanoparticles could be adjusted by changing the deposition time of the Ag element. Furthermore, after depositing the Au film on the surface of the porous nanoparticle arrays, their surface changed from hydrophilic to hydrophobic. The hydrophobic surface can drive target molecules to locally aggregate. Meanwhile, the hydrophobic surface also possessed a large number of active "hot spots" due to the porous structure. For these reasons, the porous Au-Ag alloy nanoparticle arrays can enable rapid and trace SERS detection, which provide the material basis for the subsequent construction of the high-quality SERS substrate.

The chromatin remodeling protein BRG1 regulates HSC-myofibroblast differentiation and liver fibrosis.

Excessive fibrogenic response in the liver disrupts normal hepatic anatomy and function heralding such end-stage liver diseases as hepatocellular carcinoma and cirrhosis. Myofibroblasts, derived primarily from hepatic stellate cells (HSCs), are the effector of liver fibrosis. In the present study we investigated the mechanism by which Brahma-related gene 1 (BRG1, encoded by Smarca4) regulates HSC-myofibroblast transition and the implication in intervention against liver fibrosis. We report that BRG1 expression was elevated during HSC maturation in cell culture, in animal models, and in human cirrhotic liver biopsy specimens. HSC-specific deletion of BRG1 attenuated liver fibrosis in several different animal models. In addition, BRG1 ablation in myofibroblasts ameliorated liver fibrosis. RNA-seq identified IGFBP5 as a novel target for BRG1. Over-expression of IGFBP5 partially rescued the deficiency in myofibroblast activation when BRG1 was depleted. On the contrary, IGFBP5 knockdown suppressed HSC-myofibroblast transition in vitro and mollified liver fibrosis in mice. Mechanistically, IGFBP5 interacted with Bat3 to stabilize the Bat3-TßR complex and sustain TGF-ß signaling. In conclusion, our data provide compelling evidence that BRG1 is a pivotal regulator of liver fibrosis by programming HSC-myofibroblast transition.

Investigation and prediction of the biotoxicity of Cu2+ to Chlorella vulgaris: modification of the biotic ligand model.

The increased copper ion (Cu2+) concentrations in aquatic ecosystem significantly influence the environmental quality and ecosystem safety, while information on the Cu2+ biotoxicity to aquatic microorganisms and the models for biotoxicity prediction are still unclear. In this study, the toxicities of Cu2+ to Chlorella vulgaris under different environmental conditions (e.g., Na+, K+, Ca2+, Mg2+, pH, and dissolved organic matter) were explored, with the experimental results in comparison with those predicted by the biotic ligand model (BLM). Results showed that increased Cu2+ concentration caused obvious toxicities to C. vulgaris, whereas the commonly occurring cations and dissolved organic matters can protect the metabolism system of C. vulgaris. The presence of extracellular polymeric substances (EPS) matrix can alleviate the biotoxicity via increasing the surface biosorption but decreasing cell internalization of Cu2+ in C. vulgaris. Due to the presence of EPS matrix, the experimental biotoxicity results under each condition were significantly lower than those predicted by the BLM model, which was thus modified via taking the EPS matrix as the supplement of allochthonous organic matters. After that, the modified BLM was characterized with a higher degree of precision and can be used in natural waters for biotoxicity prediction. Results obtained can enhance our insights into the ecological effects and biotoxicity prediction of heavy metals in natural aquatic ecosystems.

Carboxymethyl Cellulose/Polyacrylamide/Fe3O4 Magnetic Ion Imprinting Biosorbent for Removal and Recovery of La3.

To use resources rationally, the recovery and recycling of rare earth (RE) from industrial sewage have attracted a lot of attention. Herein, a polymer adsorbent CMC/PAM/Fe3O4 (CPF) was synthesized from renewable carboxymethyl cellulose (CMC), polyacrylamide (PAM), and Fe3O4 by the template of La3+ using ion imprinting technology. The CPF was characterized with X-ray diffraction (XRD), IR, X-ray photoelectron spectroscopy (XPS), and scanning electron microscope (SEM), and results show that PAM and CMC can crosslink with each other and form copolymers with Fe3O4 particles dispersing in it. The adsorption properties for the template ions La3+ were fully studied. It is found that CPF exhibited good adsorption performance with an adsorption capacity of 34.6 mg·g-1. Cycling experiments show that CPF still has high efficiency even after 5 cycles. Meanwhile, the desorption rate can reach more than 98%. The low wastage and high adsorption/desorption efficiency would enable CPF to be a good candidate adsorbent for removal/recovery of La3+ from industrial sewage.

Vine tea extract ameliorated acute liver injury by inhibiting hepatic autophagy and reversing abnormal bile acid metabolism.

Gut microbiota disturbance, autophagy dysregulation, and accumulation of hepatic bile acids (BAs) are essential features of liver injury. Therefore, regulating autophagy and BA metabolism are potential strategies for treating liver diseases. Vine tea has been seen beyond a pleasant tea in food science. Our previous study found that vine tea extract (VTE) intervention alleviated acute liver injury (ALI) by restoring gut microbiota dysbiosis. In this study, we aim to investigate the effect of VTE on carbon tetrachloride (CCl4)-induced hepatic autophagy and BA metabolism disorder in mice. The results showed that VTE effectively suppressed CCl4-induced liver fibrosis and hepatic autophagy. LC-MS/MS assay suggested that VTE affected fecal BA production by reducing the fecal BA levels and improving cholestasis in ALI mice. Besides, VTE inhibited BA synthesis, promoted BA transport in the liver, and enhanced BA reabsorption in the ileum through the farnesoid X receptor (FXR)-related signaling pathway. The hepatic expressions of Fxr and Abca1 were elevated by VTE. Finally, the depletion of gut microbiota in ALI mice had a negative impact on abnormal autophagy and BA metabolism. It was also noted that the administration of VTE did not provide any additional improvement in this regard. Overall, VTE ameliorated ALI by reversing hepatic autophagy and abnormal BA metabolism, and the beneficial effects of VTE on liver injury depended on the existence of gut microbiota.

Effects of released organic components of solid carbon sources on denitrification performance and the related mechanism.

Here, a hybrid scaffold of polyvinyl alcohol/sodium alginate (PVA/SA) was used to prepare solid carbon sources (SCSs) for treating low carbon/nitrogen wastewater. The four SCSs were divided into two groups, biodegradable polymers group (including polyvinyl alcohol-sodium alginate (PS) and PS-PHBV (PP), and blended SCSs (PS-PHBV-wood chips (PPW) and PS-PHBV-wheat straw (PPS)). After the leaching experiments, no changes occurred in elemental composition and functional groups of the SCSs, and the released dissolved organic matter showed a lower degree of humification and higher content of labile molecules in the blended SCSs groups using EEM and FT-ICR-MS. The denitrification performance of the blended SCSs was higher, with nitrate removal efficiency over 84%. High-throughput sequencing confirmed PPW had the highest alpha-diversity, and the microbial community structure significantly varied among SCSs. Results of functional enzymes and genes show the released carbon components directly affect the NADH level and electron transfer efficiency, ultimately influencing denitrification performance.

Phase compensation algorithm based on image segmentation in dual-wavelength holographic microscopy.

In order to solve the problem of phase compensation errors in the traditional 2π phase compensation method caused by a rough surface and complex structure of objects in dual-wavelength digital holographic microscopy, a phase compensation algorithm based on image segmentation was proposed. First, the phase less than zero in the phase obtained by an equivalent wavelength is compensated for by adding 2π initially. Then the phase after the initial compensation is binarized, and the small connected areas in the binarized graph are removed, so as to obtain a new binarized graph. Finally, according to the two binarized graphs, the phase of the object after the initial 2π phase compensation is recompensated for in different regions, so as to obtain the continuous phase distribution of the object. Based on the dual-wavelength digital holographic microscopy experimental system with an adjustable equivalent wavelength, the proposed algorithm is used to perform three-dimensional imaging of the channel of the microfluidic chip. The experimental results show that the proposed method can effectively obtain the continuous real phase of the object when the structure of the object is known, so as to obtain a more accurate and reliable three-dimensional topography of the object. The above results provide a new idea for the high-quality three-dimensional imaging of the microfluidic system.

Exosome delivery to the testes for dmrt1 suppression: A powerful tool for sex-determining gene studies.

Exosomes are endosome-derived extracellular vesicles about 100 nm in diameter. They are emerging as promising delivery platforms due to their advantages in biocompatibility and engineerability. However, research into and applications for engineered exosomes are still limited to a few areas of medicine in mammals. Here, we expanded the scope of their applications to sex-determining gene studies in early vertebrates. An integrated strategy for constructing the exosome-based delivery system was developed for efficient regulation of dmrt1, which is one of the most widely used sex-determining genes in metazoans. By combining classical methods in molecular biology and the latest technology in bioinformatics, isomiR-124a was identified as a dmrt1 inhibitor and was loaded into exosomes and a testis-targeting peptide was used to modify exosomal surface for efficient delivery. Results showed that isomiR-124a was efficiently delivered to the testes by engineered exosomes and revealed that dmrt1 played important roles in maintaining the regular structure and function of testis in juvenile fish. This is the first de novo development of an exosome-based delivery system applied in the study of sex-determining gene, which indicates an attractive prospect for the future applications of engineered exosomes in exploring more extensive biological conundrums.

Novel pH-responsive E-selectin targeting natural polysaccharides hybrid micelles for diabetic nephropathy.

Diabetic nephropathy (DN) is an important complication of diabetes and is the main cause of end-stage renal disease. The pathogenesis of DN is complex, including glucose and lipid metabolism disorder, inflammation, and so on. Novel hybrid micelles loaded Puerarin (Pue) based on Angelica sinensis polysaccharides (ASP) and Astragalus polysaccharide (APS) were fabricated with pH-responsive ASP-hydrazone-ibuprofen (BF) materials (ASP-HZ-BF, SHB) and sialic acid (SA) modified APS-hydrazone-ibuprofen materials (SA/APS-HZ-BF, SPHB) by thin-film dispersion method. The SA in hybrid micelles can specifically bind to the E-selectin receptor which is highly expressed in inflammatory vascular endothelial cells. The loaded Pue could be accurately delivered to the inflammatory site of the kidney in response to the low pH microenvironment. Overall, this study provides a promising strategy for developing hybrid micelles based on natural polysaccharides for the treatment of diabetic nephropathy by inhibiting renal inflammatory reactions, and antioxidant stress.