Triangle-toothed gear occlude-guided universal nanotechnology constructs 3D symmetric DNA polyhedra with high assembly efficiency for precision cancer therapy.

Chemotherapy is commonly used to treat malignant tumors. However, conventional chemotherapeutic drugs often cannot distinguish between tumor and healthy cells, resulting in adverse effects and reduced therapeutic efficacy. Therefore, zigzag-shaped gear-occlude-guided cymbal-closing (ZGC) DNA nanotechnology was developed based on the mirror-symmetry principle to efficiently construct symmetric DNA polyhedra. This nanotechnology employed simple mixing steps for efficient sequence design and assembly. A targeting aptamer was installed at a user-defined position using an octahedron as a model structure. Chemotherapeutic drug-loaded polyhedral objects were subsequently delivered into tumor cells. Furthermore, anticancer drug-loaded DNA octahedra were intravenously injected into a HeLa tumor-bearing mouse model. Assembly efficiency was almost 100 %, with no residual building blocks identified. Moreover, this nanotechnology required a few DNA oligonucleotides, even for complex polyhedrons. Symmetric DNA polyhedrons retained their structural integrity for 24 h in complex biological environments, guaranteeing prolonged circulation without drug leakage in the bloodstream and promoting efficient accumulation in tumor tissues. In addition, DNA octahedra were cleared relatively slowly from tumor tissues. Similarly, tumor growth was significantly inhibited in vivo, and a therapeutic outcome comparable to that of conventional gene-chemo combination therapy was observed. Moreover, no systemic toxicity was detected. These findings indicate the potential application of ZGC DNA nanotechnology in precision medicine.

Carbon-anchoring synthesis of Pt1Ni1@Pt/C core-shell catalysts for stable oxygen reduction reaction.

Proton-exchange-membrane fuel cells demand highly efficient catalysts for the oxygen reduction reaction, and core-shell structures are known for maximizing precious metal utilization. Here, we reported a controllable "carbon defect anchoring" strategy to prepare Pt1Ni1@Pt/C core-shell nanoparticles with an average size of ~2.6 nm on an in-situ transformed defective carbon support. The strong Pt-C interaction effectively inhibits nanoparticle migration or aggregation, even after undergoing stability tests over 70,000 potential cycles, resulting in only 1.6% degradation. The stable Pt1Ni1@Pt/C catalysts have high oxygen reduction reaction mass activity and specific activity that reach 1.424 ± 0.019 A/mgPt and 1.554 ± 0.027 mA/cmPt2 at 0.9 V, respectively, attributed to the optimal compressive strain. The experimental results are generally consistent with the theoretical predictions made by our comprehensive microkinetic model which incorporates essential kinetics and thermodynamics of oxygen reduction reaction. The consistent results obtained in our study provide compelling evidence for the high accuracy and reliability of our model. This work highlights the synergy between theory-guided catalyst design and appropriate synthetic methodologies to translate the theory into practice, offering valuable insights for future catalyst development.

Vitamin U alleviates AFB1-induced hepatotoxicity in pregnant and lactating mice by regulating the Nrf2/Hmox1 pathway.

This study investigated the protective effect of Vitamin U on liver injury induced by aflatoxin B1 (AFB1) in maternal mice. 25 pregnant ICR mice were randomly divided into five groups: the AFB1 group (AF, 0.3 mg AFB1/kg b.w.), the Vitamin U group (U, 50 mg Vitamin U/kg b.w.), the AFB1 + Vitamin U group (AU, 50 mg Vitamin U /kg b.w. + 0.3 mg AFB1/kg b.w.), the control group (DMSO), and the MOCK group (distilled water). They were administered substances by gavage every day for 28 days. Results indicated that exposure to AFB1 increased the liver index and caused histological disruptions. Elevated serum levels of ALT and ALP were observed, along with a significant increase in liver MDA content and a decrease in GSH-Px and T-SOD levels. Moreover, the Keap1 and Hmox1 gene was downregulated with statistical significance, while the IL1ß and TNFα gene were significantly upregulated. Vitamin U was demonstrated by the organized structure of liver cells in tissue slices, effectively reducing liver cell necrosis. This intervention was associated with a significant decrease in serum ALT and ALP activities, as well as a significant decrease in liver MDA content. Additionally, there were significant increases in liver T-SOD and GSH-Px levels, along with upregulation of mRNA and protein expression of Nfr2, Hmox1 and Keap1, and downregulation of mRNA expression of the IL1ß gene. In summary, Vitamin U mitigated oxidative stress-induced liver injury by modulating the Nrf2/Hmox1 signaling pathway and inflammatory factors affected by AFB1.

Decoding the temporal structures and interactions of multiple face dimensions using optically pumped magnetometer magnetoencephalography (OPM-MEG).

Humans possess a remarkable ability to rapidly access diverse information from others' faces with just a brief glance, which is crucial for intricate social interactions. While previous studies using event-related potentials/fields have explored various face dimensions during this process, the interplay between these dimensions remains unclear. Here, by applying multivariate decoding analysis to neural signals recorded with optically pumped magnetometer magnetoencephalography (OPM-MEG), we systematically investigated the temporal interactions between invariant and variable aspects of face stimuli, including race, gender, age and expression. First, our analysis revealed unique temporal structures for each face dimension with high test-retest reliability. Notably, expression and race exhibited a dominant and stably maintained temporal structure according to temporal generalization analysis. Further exploration into the mutual interactions among face dimensions uncovered age effects on gender and race, as well as expression effects on race, during the early stage (around 200-300 ms post face presentation). Additionally, we observed a relatively late effect of race on gender representation, peaking around 350 ms after stimulus onset. Taken together, our findings provide novel insights into the neural dynamics underlying the multi-dimensional aspects of face perception and illuminate the promising future of utilizing OPM-MEG for exploring higher-level human cognition.Significance statement In everyday social activities, people can quickly interpret a wide range of information from others' faces. Although converging evidence has shed light upon the neural substrates underpinning the perception of invariant and variable aspects of faces, such as race, gender, age and expression, it is still not fully understood how the information of one face dimension alters the perception of another. In this study, we utilized multivariate decoding analysis on neural activity captured through OPM-MEG during face perception. Our approach enabled a comprehensive exploration of the temporal interactions among different face dimensions, providing an improved understanding of the temporally structured neural dynamics that support the multi-dimensional face perception in the human brain.

Symmetry Donor-Acceptor Molecule Regulating Hydrogen-Bonding Network for Improved Metal Zinc Anode.

The issues of zinc dendrites and side reactions caused by active water molecules have seriously affected the development of aqueous zinc batteries (AZBs). Herein, a symmetry hydrogen-bond donor-acceptor molecule additive named 1,3-bis(hydroxymethyl)urea (BHMU) can preferentially adsorb on the anode surface and lock up water molecules through hydrogen bonding, thus isolating water molecules and reducing side reactions caused by active water molecules. With these advantages, the mixed electrolyte containing BHMU additive impels a reversible Zn anode with a high Coulombic efficiency (99.7% over 1000 cycles at 1 mA cm-2), while it also enables a stable symmetric cell operated at 1 mA cm-2 (1 mAh cm-2, 6.89% DODZn) for 2250 h and 10 mA cm-2 (10 mAh cm-2, 68.9% DODZn) for 350 h. More importantly, the Zn||PTO full battery also delivered superior cycling stability and higher capacity after 3000 consecutive 3000 cycles of circulation at 5 A g-1. This study has great significance for the use of symmetry donor-acceptor molecules to modulate the solvation structure and the interface stability of the Zn anode in aqueous electrolytes.

Development and collaborative validation of an event-specific quantitative real-time PCR method for detection of genetically modified CC-2 maize.

As one of the developed genetically modified (GM) maize varieties in China, CC-2 has demonstrated promising commercial prospects during demonstration planting. The establishment of detection methods is a technical prerequisite for effective supervision and regulation of CC-2 maize. In this study, we have developed an event-specific quantification method that targets the junction region between the exogenous gene and the 5' flanking genomic DNA (gDNA) of CC-2. The accuracy and precision of this method were evaluated across high, medium, and low levels of CC-2 maize content, revealing biases within ±25% and satisfactory precision data. Additionally, we determined the limits of quantification of the method to be 0.05% (equivalent to 20 copies) of the CC-2 maize. A collaborative trial further confirmed that our event-specific method for detecting CC-2 produces reliable, comparable, and reproducible results when applied to five different samples provided by various sources. Furthermore, we calculated the expanded uncertainty associated with determining the content level of CC-2 in these samples.

Inversion model of soil salinity in alfalfa covered farmland based on sensitive variable selection and machine learning algorithms.

Purpose: Timely and accurate monitoring of soil salinity content (SSC) is essential for precise irrigation management of large-scale farmland. Uncrewed aerial vehicle (UAV) low-altitude remote sensing with high spatial and temporal resolution provides a scientific and effective technical means for SSC monitoring. Many existing soil salinity inversion models have only been tested by a single variable selection method or machine learning algorithm, and the influence of variable selection method combined with machine learning algorithm on the accuracy of soil salinity inversion remain further studied. Methods: Firstly, based on UAV multispectral remote sensing data, by extracting the spectral reflectance of each sampling point to construct 30 spectral indexes, and using the pearson correlation coefficient (PCC), gray relational analysis (GRA), variable projection importance (VIP), and support vector machine-recursive feature elimination (SVM-RFE) to screen spectral index and realize the selection of sensitive variables. Subsequently, screened and unscreened variables as model input independent variables, constructed 20 soil salinity inversion models based on the support vector machine regression (SVM), back propagation neural network (BPNN), extreme learning machine (ELM), and random forest (RF) machine learning algorithms, the aim is to explore the feasibility of different variable selection methods combined with machine learning algorithms in SSC inversion of crop-covered farmland. To evaluate the performance of the soil salinity inversion model, the determination coefficient (R2), root mean square error (RMSE) and performance deviation ratio (RPD) were used to evaluate the model performance, and determined the best variable selection method and soil salinity inversion model by taking alfalfa covered farmland in arid oasis irrigation areas of China as the research object. Results: The variable selection combined with machine learning algorithm can significantly improve the accuracy of remote sensing inversion of soil salinity. The performance of the models has been improved markedly using the four variable selection methods, and the applicability varied among the four methods, the GRA variable selection method is suitable for SVM, BPNN, and ELM modeling, while the PCC method is suitable for RF modeling. The GRA-SVM is the best soil salinity inversion model in alfalfa cover farmland, with Rv 2 of 0.8888, RMSEv of 0.1780, and RPD of 1.8115 based on the model verification dataset, and the spatial distribution map of soil salinity can truly reflect the degree of soil salinization in the study area. Conclusion: Based on our findings, the variable selection combined with machine learning algorithm is an effective method to improve the accuracy of soil salinity remote sensing inversion, which provides a new approach for timely and accurate acquisition of crops covered farmland soil salinity information.

The Differences in Parameters in Ultrasound Imaging and Biomechanical Properties of the Quadriceps Femoris with Unilateral Knee Osteoarthritis in the Elderly: A Preliminary Observational Study.

Purpose: Our study aims to evaluate differences in muscle parameters of the quadriceps muscles in patients with knee osteoarthritis (KOA) in older adults. Methods: The study included 40 patients diagnosed with unilateral knee osteoarthritis in the KOA group (KG) and 40 asymptomatic elderly individuals in the control group (CG). Muscle ultrasonic mean echo intensity and shear modulus, as well as tone and stiffness of the rectus femoris (RF), vastus medialis (VM), and vastus lateralis (VL) were analyzed. Additionally, clinical correlations were performed. Results: In the KG group, there were significant differences in echo intensity, shear modulus, and tone between the affected and unaffected sides for RF (p=0.003, 0.019, 0.014), while VM showed significant differences in shear modulus and tone (p=0.006, 0.002). Additionally, VL exhibited significant differences in echo intensity, shear modulus, and stiffness (p=0.007, 0.006, 0.010). Compared to the CG group, the KG group showed significant differences in echo intensity of the affected side RF (p=0.001). VM exhibited statistically significant differences in echo intensity and shear modulus (p < 0.001, p=0.008), while VL showed statistically significant differences in echo intensity, tone, and stiffness (p < 0.001, p=0.028, p < 0.001). The correlation results showed that patients with unilateral KOA, VM, and VL echo intensity were correlated with K-L grade (r = 0.443, p=0.004; r = 0.469, p=0.002). The tone of VL was correlated with VAS and WOMAC (r = 0.327, p=0.039; r = 0.344, p=0.030). Conclusion: The parameters of the quadriceps femoris muscle exhibit asymmetry between the affected and unaffected sides in patients with unilateral KOA, as well as a difference between the dominant side of healthy older individuals and the affected side of KOA.

A Lightweight Pathological Gait Recognition Approach Based on a New Gait Template in Side-View and Improved Attention Mechanism.

As people age, abnormal gait recognition becomes a critical problem in the field of healthcare. Currently, some algorithms can classify gaits with different pathologies, but they cannot guarantee high accuracy while keeping the model lightweight. To address these issues, this paper proposes a lightweight network (NSVGT-ICBAM-FACN) based on the new side-view gait template (NSVGT), improved convolutional block attention module (ICBAM), and transfer learning that fuses convolutional features containing high-level information and attention features containing semantic information of interest to achieve robust pathological gait recognition. The NSVGT contains different levels of information such as gait shape, gait dynamics, and energy distribution at different parts of the body, which integrates and compensates for the strengths and limitations of each feature, making gait characterization more robust. The ICBAM employs parallel concatenation and depthwise separable convolution (DSC). The former strengthens the interaction between features. The latter improves the efficiency of processing gait information. In the classification head, we choose to employ DSC instead of global average pooling. This method preserves the spatial information and learns the weights of different locations, which solves the problem that the corner points and center points in the feature map have the same weight. The classification accuracies for this paper's model on the self-constructed dataset and GAIT-IST dataset are 98.43% and 98.69%, which are 0.77% and 0.59% higher than that of the SOTA model, respectively. The experiments demonstrate that the method achieves good balance between lightweightness and performance.

Biocatalytic Desymmetrization for the Atroposelective Synthesis of Axially Chiral Biaryls Using an Engineered Imine Reductase.

The enzymatic atroposelective synthesis of biaryl compounds is relatively rare, despite considerable attention received by biocatalysis in the academic and industrial sectors. Imine reductases (IREDs) are an important class of enzymes that have been applied in the asymmetric synthesis of chiral amine building blocks. In this study, two IREDs (IR140 and IR189) were identified to catalyze the efficient desymmetrization of biaryls utilizing various amine donors. Further protein engineering enabled the identification of variants (IR189 M8-M9 and IR189 M13-M14) that are able to catalyze the formation of both (R) and (S) atropisomers in excellent yields and atroposelectivities (24 examples, up to 99 % ee and yield). The absolute configuration and rotational barriers were confirmed, and the reactions were readily scaled up to allow isolation of the atropisomeric product in 99 % ee and 82 % yield. The optically pure biaryl amines were further derivatized into various synthetically useful atropisomers. To shed light on the molecular recognition mechanisms, molecular dynamics (MD) simulations were performed, offering plausible explanations for the improved atroposelectivity and enzymatic activity. The current strategy expands the scope of the IRED-catalyzed synthesis of axially chiral biaryl amines, contributing significantly to the field of atroposelective biocatalysis.

Peripheral blood-derived PD-1/CD28-CD19-CAR-modified PD-1+ T-cell therapy in patients with solid tumors.

T cells expressing PD-1 in the peripheral blood (PB) of patients with tumors possess therapeutic potential; however, the immunosuppressive, PD1-triggered signaling pathway and limited proliferative capacity of PD-1+ T cells present challenges to their therapeutic application. Here, we observed no discernible distinction between PD-1+ and PD-1- T cells in terms of clonal overlap. However, CD8+PD-1+ T cells from PB and tumor tissues exhibited tighter clustering based on clone size. Single-cell RNA sequencing analysis showed that PD-1+ T cells from PB highly expressed cytotoxicity-related genes and were enriched for T cell activation-related pathways compared with PD-1- T cells from PB or tumor tissues. Consistent with this, PB-derived PD-1+ T cells exhibited strong cytotoxicity towards autologous tumor cells and tumor cell lines. To augment PD-1+ T-cell activity against solid tumors in vivo, we introduced a PD-1/CD28 fusion receptor combined with a CD19 chimeric antigen receptor (CAR) into PD-1+ T cells, which were then expanded in vitro. The modified PD-1+ T cells exhibited superior proliferation and antitumor abilities in vitro. In addition, four patients with cancer were infused with autologous PD-1/CD28-CD19-CAR PD-1+ T cells. None of these patients experienced severe side effects and one patient with melanoma achieved a complete response that was maintained for 6.7 months. The three other patients had stable disease. Collectively, these results suggested that cell therapy with modified PB-derived PD-1+ T cells is both safe and effective, and it may constitute a promising treatment strategy for cancer patients.

Wireless optically pumped magnetometer MEG.

The current magnetoencephalography (MEG) systems, which rely on cables for control and signal transmission, do not fully realize the potential of wearable optically pumped magnetometers (OPM). This study presents a significant advancement in wireless OPM-MEG by reducing magnetization in the electronics and developing a tailored wireless communication protocol. Our protocol effectively eliminates electromagnetic interference, particularly in the critical frequency bands of MEG signals, and accurately synchronizes the acquisition and stimulation channels with the host computer's clock. We have successfully achieved single-channel wireless OPM-MEG measurement and demonstrated its reliability by replicating three well-established experiments: The alpha rhythm, auditory evoked field, and steady-state visual evoked field in the human brain. Our prototype wireless OPM-MEG system not only streamlines the measurement process but also represents a major step forward in the development of wearable OPM-MEG applications in both neuroscience and clinical research.

Stereoselective Synthesis of Oxetanes Catalyzed by an Engineered Halohydrin Dehalogenase.

Although biocatalysis has garnered widespread attention in both industrial and academic realms, the enzymatic synthesis of chiral oxetanes remains an underdeveloped field. Halohydrin dehalogenases (HHDHs) are industrially relevant enzymes that have been engineered to accomplish the reversible transformation of epoxides. In this study, a biocatalytic platform was constructed for the stereoselective kinetic resolution of chiral oxetanes and formation of 1,3-disubstituted alcohols. HheC from Agrobacterium radiobacter AD1 was engineered to identify key variants capable of catalyzing the dehalogenation of γ-haloalcohols (via HheC M1-M3) and ring opening of oxetanes (via HheC M4-M5) to access both (R)- and (S)-configured products with high stereoselectivity and remarkable catalytic activity, yielding up to 49 % with enantioselectivities exceeding 99 % ee and E>200. The current strategy is broadly applicable as demonstrated by expansion of the substrate scope to include up to 18 examples for dehalogenation and 16 examples for ring opening. Additionally, the functionalized products are versatile building blocks for pharmaceutical applications. To shed light on the molecular recognition mechanisms for the relevant variants, molecular dynamic (MD) simulations were performed. The current strategy expands the scope of HHDH-catalyzed chiral oxetane ring construction, offering efficient access to both enantiomers of chiral oxetanes and 1,3-disubstituted alcohols.

Synergistic Sr Activation and Cr Buffering Effect on RuO2 Electronic Structures for Enhancing the Acidic Oxygen Evolution Reaction.

The oxygen evolution reaction (OER) performance of ruthenium-based oxides strongly correlates with the electronic structures of Ru. However, the widely adopted monometal doping method unidirectionally regulates only the electronic structures, often failing to balance the activity and stability. Here, we propose an "elastic electron transfer" strategy to achieve bidirectional optimization of the electronic structures of Sr, Cr codoped RuO2 catalysts for acidic OER. The introduction of electron-withdrawing Sr intrinsically activates the Ru sites by increasing the oxidation state of Ru. Simultaneously, Cr acts as an electron buffer, donating electrons to Ru in the presence of Sr in the as-prepared catalysts and absorbing excess electrons from Sr leaching during the OER. Such a bidirectional regulation feature of Cr prevents overoxidation of Ru and maintains its high oxidation state during the OER. The optimal Ru3Cr1Sr0.175 catalyst exhibits a low overpotential (214 mV @ 10 mA cm-2) and excellent stability (over 300 h).

Research into the Applications of a Multi-Scale Feature Fusion Model in the Recognition of Abnormal Human Behavior.

Due to the increasing severity of aging populations in modern society, the accurate and timely identification of, and responses to, sudden abnormal behaviors of the elderly have become an urgent and important issue. In the current research on computer vision-based abnormal behavior recognition, most algorithms have shown poor generalization and recognition abilities in practical applications, as well as issues with recognizing single actions. To address these problems, an MSCS-DenseNet-LSTM model based on a multi-scale attention mechanism is proposed. This model integrates the MSCS (Multi-Scale Convolutional Structure) module into the initial convolutional layer of the DenseNet model to form a multi-scale convolution structure. It introduces the improved Inception X module into the Dense Block to form an Inception Dense structure, and gradually performs feature fusion through each Dense Block module. The CBAM attention mechanism module is added to the dual-layer LSTM to enhance the model's generalization ability while ensuring the accurate recognition of abnormal actions. Furthermore, to address the issue of single-action abnormal behavior datasets, the RGB image dataset RIDS (RGB image dataset) and the contour image dataset CIDS (contour image dataset) containing various abnormal behaviors were constructed. The experimental results validate that the proposed MSCS-DenseNet-LSTM model achieved an accuracy, sensitivity, and specificity of 98.80%, 98.75%, and 98.82% on the two datasets, and 98.30%, 98.28%, and 98.38%, respectively.

Rationally Engineered Novel Glycosyltransferase UGT74DD1 from Siraitia grosvenorii Catalyzes the Generation of the Sweetener Mogroside III.

Mogrosides are natural compounds highly valued in the food sector for their exceptional sweetness. Here, we report a novel O-glycosyltransferase (UGT74DD1) from Siraitia grosvenorii that catalyzes the conversion of mogrol to mogroside IIE. Site-directed mutagenesis yielded the UGT74DD1-W351A mutant, which exhibited the new capability to transform mogroside IIE into the valuable sweetener mogroside III, but with low catalytic activity. Subsequently, using structure-guided directed evolution with combinatorial active-site saturation testing, the superior mutant M6 (W351A/Q373 K/E49H/Q335W/S278C/D17F) were obtained, which showed a 46.1-fold increase in catalytic activity compared to UGT74DD1-W351A. Molecular dynamics simulations suggested that the enhanced activity and extended substrate profiles of M6 are due to its enlarged substrate-binding pocket and strengthened enzyme-substrate hydrogen bonding interactions. Overall, we redesigned UGT74DD1, yielding mutants that catalyze the conversion of mogrol into mogroside III. This study thus broadens the toolbox of UGTs capable of catalyzing the formation of valuable polyglycoside compounds.

Double-edge scan wavefront metrology and its application in crystal diffraction wavefront measurements.

Achieving diffraction-limited performance in fourth-generation synchrotron radiation sources demands monochromator crystals that can preserve the wavefront across an unprecedented extensive range. There is an urgent need for techniques of absolute crystal diffraction wavefront measurement. At the Beijing Synchrotron Radiation Facility (BSRF), a novel edge scan wavefront metrology technique has been developed. This technique employs a double-edge tracking method, making diffraction-limited level absolute crystal diffraction wavefront measurement a reality. The results demonstrate an equivalent diffraction surface slope error below 70 nrad (corresponding to a wavefront phase error of 4.57% λ) r.m.s. within a nearly 6 mm range for a flat crystal in the crystal surface coordinate. The double-edge structure contributes to exceptional measurement precision for slope error reproducibility, achieving levels below 15 nrad (phase error reproducibility < λ/100) even at a first-generation synchrotron radiation source. Currently, the measurement termed double-edge scan (DES) has already been regarded as a critical feedback mechanism in the fabrication of next-generation crystals.

Chromatin accessibility and transcriptional landscape in PK-15 cells during early exposure to Aflatoxin B1.

Aflatoxin B1 (AFB1) not only causes significant losses in livestock production but also poses a serious threat to human health. It is the most carcinogenic among known chemicals. Pigs are more susceptible to AFB1 and experience a higher incidence. However, the molecular mechanism of the toxic effect of AFB1 remains unclear. In this study, we used assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA-seq to uncover chromatin accessibility and gene expression dynamics in PK-15 cells during early exposure to AFB1. We observed that the toxic effects of AFB1 involve signaling pathways such as p53, PI3K-AKT, Hippo, MAPK, TLRs, apoptosis, autophagy, and cancer pathways. Basic leucine zipper (bZIP) transcription factors (TFs), including AP-1, Fos, JunB, and Fra2, play a crucial role in regulating the biological processes involved in AFB1 challenge. Several new TFs, such as BORIS, HNF1b, Atf1, and KNRNPH2, represent potential targets for the toxic mechanism of AFB1. In addition, it is crucial to focus on the concentration of intracellular zinc ions. These findings will contribute to a better understanding of the mechanisms underlying AFB1-induced nephrotoxicity and offer new molecular targets.

Icariin attenuates asthmatic airway inflammation via modulating alveolar macrophage activation based on network pharmacology and in vivo experiments.

BACKGROUND: Icariin (ICA) inhibits inflammatory response in various diseases, but the mechanism underlying ICA treating airway inflammation in asthma needs further understood. We aimed to predict and validate the potential targets of ICA against asthma-associated airway inflammation using network pharmacology and experiments. METHODS: The ovalbumin-induced asthma-associated airway inflammation mice model was established. The effects of ICA were evaluated by behavioral, airway hyperresponsiveness, lung pathological changes, inflammatory cell and cytokines counts. Next, the corresponding targets of ICA were mined via the SEA, CTD, HERB, PharmMapper, Symmap database and the literature. Pubmed-Gene and GeneCards databases were used to screen asthma and airway inflammation-related targets. The overlapping targets were used to build an interaction network, analyze gene ontology and enrich pathways. Subsequently, flow cytometry, quantitative real-time PCR and western blotting were employed for validation. RESULTS: ICA alleviated the airway inflammation of asthma; 402 targets of ICA, 5136 targets of asthma and 4531 targets of airway inflammation were screened; 216 overlapping targets were matched and predicted ICA possesses the potential to modulate asthmatic airway inflammation by macrophage activation/polarization. Additionally, ICA decreased M1 but elevated M2. Potential targets that were disrupted by asthma inflammation were restored by ICA treatment. CONCLUSIONS: ICA alleviates airway inflammation in asthma by inhibiting the M1 polarization of alveolar macrophages, which is related to metabolic reprogramming. Jun, Jak2, Syk, Tnf, Aldh2, Aldh9a1, Nos1, Nos2 and Nos3 represent potential targets of therapeutic intervention. The present study enhances understanding of the anti-airway inflammation effects of ICA, especially in asthma.