Cobalt-Catalyzed Asymmetric Migratory Nozaki-Hiyama-Kishi Coupling.

Selective functionalization of ubiquitous C-H bonds based on 1,n-metal migration provides an attractive and sustainable route to access complex molecules from readily available precursors. Herein, we report a Co-catalyzed asymmetric reductive migratory Nozaki-Hiyama-Kishi (NHK) coupling between two readily available electrophiles, aryl (pseudo)halides and aldehydes, via an unprecedented through-space aryl-to-alkenyl 1,4-cobalt/hydride shift. The judicious choice of ligands is crucial for selectivity, leading to either ipso- or migratory NHK products with exquisite control of regio-, E/Z-, and enantioselectivity. Enabled by a ligand relay catalytic strategy, this platform has been further extended to aryl-to-aryl asymmetric migratory NHK coupling. These high-value NHK adducts, including α-chiral allylic alcohols and benzyl alcohols, are readily convertible to a variety of useful synthons.

Design and Synthesis of Cytotoxic Water-Soluble Rocaglaol Derivatives against HEL Cells by Inhibiting Fli-1.

Rocaglaol, embedding a cyclopenta[b]benzofuran scaffold, was isolated mainly from the plants of Aglaia and exhibited nanomolar level antitumor activity. However, the drug-like properties of these compounds are poor. To improve the physicochemical properties of rocaglaol, 36 nitrogen-containing phenyl-substituted rocaglaol derivatives were designed and synthesized. These derivatives were tested for the inhibitory effects on three tumor cell lines, HEL, MDA-231, and SW480, using the MTT assay. Among them, 22 derivatives exhibited good cytotoxic activities with IC50 values between 0.11 ± 0.07 and 0.88 ± 0.02 µM. Fourteen derivatives exhibited stronger cytotoxicity than the positive control, adriamycin. In particular, a water-soluble derivative revealed selective cytotoxic effects on HEL cells (IC50 = 0.19 ± 0.01 µM). This compound could induce G1 cell cycle arrest and apoptosis in HEL cells. Western blot assays suggested that the water-soluble derivative could downregulate the expression of the marker proteins of apoptosis, PARP, caspase-3, and caspase-9, thus inducing apoptosis. Further CETSA and Western blot studies implied that this water-soluble derivative might be an inhibitor of friend leukemia integration 1 (Fli-1). This water-soluble derivative may serve as a potential antileukemia agent by suppressing the expression of Fli-1.

[Construction of model for multidimensional evaluation of value and risk of Chinese patent medicine].

It is the core of the development for Chinese patent medicine enterprises to cultivate large varieties of Chinese patent medicine, and the selection of potential "seed" products is the prerequisite for the cultivation strategy. By constructing the evaluation model from multiple dimensions of value and risk, we can conduct specialized evaluation of Chinese patent medicines to effectively, professionally and objectively select the "seed" products with large variety cultivation potential. In this paper, the establishment of a multidimensional evaluation system would be discussed from the aspects of drug naming and prescription composition, safety risk and supply guarantee of raw materials and medicinal materials, competition situation, access to policy catalogue, scientific and technological support, clinical evidence and recognition, systematical and standardized collection of information on product instructions, quality standards, policy catalogue, scientific and technological literature, market competition and clinical application of Chinese patent medicines. Through the objective evaluation index and the range of objective index, the multi-dimensional evaluation model on values and risks of Chinese patent medicine products was discussed. Based on this model, a batch of Chinese patent medicine products can be quickly and comprehensively analyzed, and quantitative comparison can be formed among different types and fields of products. According to the evaluation results of the model and the comprehensive evaluation of experts, high-quality "seed" products can be selec-ted, laying a solid foundation for the next step of large variety cultivation. With use of this model, we can further clarify the external competitive advantages and internal priority levels of each product, and provide support for enterprises to optimize product structure and improve product strategic layout.

Rapamycin attenuates the paraquat-induced pulmonary fibrosis through activating Nrf2 pathway.

Oxidative stress is a key regulator of idiopathic pulmonary fibrosis. Paraquat (PQ)-induced pulmonary fibrosis seriously endangers people's health. Rapamycin has been reported to alleviate PQ-induced pulmonary fibrosis, but its underlying mechanism is unclear. The nuclear factor E2-related factor 2 (Nrf2) plays an important regulatory role in the antioxidant therapy of PQ-induced pulmonary fibrosis. In this study, we tried to confirm that rapamycin attenuates PQ-induced pulmonary fibrosis by regulating Nrf2 pathway. In vivo, we proved that rapamycin could inhibit the degree of PQ-induced oxidant stress as well as enhanced the expression of Nrf2. In vitro, rapamycin decreased the upregulated effects of cell death and apoptosis, fibrosis-related factors expression and fibroblast-to-myofibroblast transformation by PQ treatment. In vivo, rapamycin treatment reduced fibrosis degree and the expression of fibrosis-related factors in lung tissues of rat treated PQ. Furthermore, we also found that Nrf2 knockdown reduced the inhibitory effect of rapamycin on PQ-induced pulmonary fibrosis, as well as decreased Nrf2 transfer from the cytoplasm into the nucleus. Our findings demonstrated that the protective effect of rapamycin is associated with the activation of the Nrf2 pathway in pulmonary fibrosis induced by PQ poisoning.

Study on the yielding behaviors of ferrofluids: a very shear thinning phenomenon.

The yielding behaviors of the ferrofluids are vital for many applications. However, previous studies have mainly focused on the magnetoviscous effect under relatively high shear rates and rarely involved the yielding process of ferrofluids under very low shear rates. In this study, ferrofluid samples of different particle volume concentrations were prepared and their shear thinning behaviors within a wide shear stress range were systematically studied under various magnetic field strengths and temperatures. The very shear thinning phenomenon of ferrofluids was first observed and its microscopic mechanism was analyzed. A precipitous fall-off stage as the mark of yielding appeared between the low shear and high shear plateaus in the viscosity curves of ferrofluids. The precipitous fall-off stage in the viscosity curves became steeper with the increase of the magnetic field strength or decrease in the temperature. For ferrofluids with relatively low particle volume concentrations, the high viscosity limit under the low shear region disappeared when temperature exceeded a certain value and was interpreted as the disappearance of the equilibrium columnar structures under high Brownian thermal interaction level. A composite Ellis model was proved to be suitable for the fitting of different types of yield stresses and a structural number, Sn was proposed for the dimensionless analysis of the shear thinning behaviors of ferrofluids. The findings in this study contribute to a better understanding of the microscopic mechanism of yielding behaviors of ferrofluids and also provide guidance for many practical applications.

[Analysis of patent data of Panax notoginseng and enlightenment of industrial development].

In order to find the trends in Panax notoginseng industries of China, a combination of data analysis and empirical analysis was applied to analyze the application of global P. notoginseng patents, the innovation field, the distribution of patent assets, the patent citation network, the distribution of enterprises, the talent team, the competition and cooperation situation based on the financial big data platform of intellectual property industry. From the perspective of industrial technology hotspots, the clinical application of P. notoginseng is becoming more and more widespread, and its clinical treatment field is further expanding. From the perspective of industrial fields, the P. notoginseng industry has gradually expanded from the traditional Chinese medicine field to food, cosmetics, beverages, tea and other daily consumer goods. From the perspective of patent quality, the average maintenance life of P. notoginseng patents of China is lower than the global level, and the value and quality of patents need to be further improved. And the quality of P. notoginseng of China related patent applications has gradually improved in recent years. We analyzed the technology, capital, and talent issues of P. notoginseng industry of China, and summarized and forecasted the status and trends of P. notoginseng industry development of China. It is considered that scientific and technological innovation has become the core engine for the development of the P. notoginseng industry and intellectual property, especially patent protection, escorted the sustainable development of the P. notoginseng industry. Based on the above analysis, several suggestions were put forward to promote the high-quality development of the P. notoginseng industry. It should strengthen scientific and technological support, especially the need for a large number of high-quality scientific and technological output, expand multi-party cooperation, build a high-level technological innovation platform for the P. notoginseng industry, guide long-term capital to continuously and stably invest, and help the P. notoginseng industry to revitalize.

Resolvin D1 Attenuates Myocardial Infarction in a Rodent Model with the Participation of the HMGB1 Pathway.

PURPOSE: Myocardial infarction (MI) is associated with high morbidity and mortality worldwide. This study aimed to explore the roles of resolvin D1 (RvD1), a metabolite of omega-3 polyunsaturated fatty acids, in protection against MI and investigate its influences on high mobility group box 1 protein (HMGB1) and related molecular mechanisms. METHODS: Three-month-old male Sprague-Dawley rats were divided into five groups: sham, MI, MI+0.02 µg RvD1, MI+0.1 µg RvD1, and MI+0.3 µg RvD1. Vehicle control or different doses of RvD1 were injected into the left ventricle (LV) cavity 5 min before MI induction. During MI induction, myocardial ischemia lasted for 45 min followed by 180 min of reperfusion. After the reperfusion, blood and LV samples were collected for biochemical examination. RESULTS: The MI group produced a significant increase in myocardial infarct size, serum cardiac biomarkers (LDH and CK-MB), proinflammatory cytokines (TNF-α and IL-6), and MDA levels, and a significant decrease in SOD level compared with the sham group. Moreover, a significant upregulation of gene and protein expressions of HMGB1 and its related TLR4 and NF-κB were observed in the MI group when compared with the sham group. Pretreatment of RvD1 ameliorated the biochemical changes caused by MI. CONCLUSIONS: Our results suggested that RvD1 pretreatment exhibited protective effects against MI through downregulation of HMGB1 and its related TLR4 and NF-κB expressions.

Influence of the Carrier Fluid Viscosity on the Rotational and Oscillatory Rheological Properties of Ferrofluids.

This work mainly presents a comprehensive experimental study on the magnetorheological behavior of ferrofluids with carrier fluids of different viscosities. Three lubrication oil based ferrofluids of different viscosities and similar saturation magnetization values were prepared and characterized. Static and dynamic rheological tests of the three ferrofluids were performed using an advanced rotational rheometer with a magnetic field generating module. According to the experimental results, the magneto viscous effect, yield stress and storage modulus increase with the viscosity of carrier fluid, indicating that the structures of ferrrofluids tend to be larger and more stable in a carrier fluid with larger viscosity. The emergence and growth of "crossover" region with the increase in carrier fluid viscosity was observed using the strain-rate frequency superposition method, which were explained according to the microscopic mechanism of magnetorheology. These findings contribute to a better understanding of the microscopic mechanism of magnetorheology and provide guidance for practical applications.

Optimal Placement of Virtual Masses for Structural Damage Identification.

Adding virtual masses to a structure is an efficient way to generate a large number of natural frequencies for damage identification. The influence of a virtual mass can be expressed by Virtual Distortion Method (VDM) using the response measured by a sensor at the involved point. The proper placement of the virtual masses can improve the accuracy of damage identification, therefore the problem of their optimal placement is studied in this paper. Firstly, the damage sensitivity matrix of the structure with added virtual masses is built. The Volumetric Maximum Criterion of the sensitivity matrix is established to ensure the mutual independence of measurement points for the optimization of mass placement. Secondly, a method of sensitivity analysis and error analysis is proposed to determine the values of the virtual masses, and then an improved version of the Particle Swarm Optimization (PSO) algorithm is proposed for placement optimization of the virtual masses. Finally, the optimized placement is used to identify the damage of structures. The effectiveness of the proposed method is verified by a numerical simulation of a simply supported beam structure and a truss structure.

Study of the thixotropic behaviors of ferrofluids.

The thixotropic behaviors of ferrofluid samples of different particle concentration were studied using different measurement methods, including the three interval thixotropic test and the hysteresis loop test. The experimental results demonstrated that ferrofluids exhibit significant thixotropic behaviors and the microstructural evolution in ferrofluids behind the macroscopic rheological mechanics is discussed. The influence of magnetic field strength, particle concentration and temperature on the thixotropy of ferrofluids was also analyzed. Microscopic ferrofluid theory was adopted to study the thixotropic behaviors of ferrofluids under different shearing conditions, indicating that different thixotropic behaviors of ferrofluids can be induced by the presence and evolution of different kinds of microstructures, such as linear chain-like and dense drop-like structures. Furthermore, a phenomenal thixotropic model was employed to analyze the experimental results, indicating that a more specific model for ferrofluids is needed. These findings contribute to a better understanding of the microscopic mechanism of the complex rheological behaviors of ferrofluids.

Rapamycin protects against paraquat-induced pulmonary fibrosis: Activation of Nrf2 signaling pathway.

Paraquat (PQ) is a widely used herbicide indeveloping countries worldwide, and pulmonary fibrosis is one of the most typical features of PQ poisoning. The molecular mechanism of PQ toxicity especially how to treat PQ-induced pulmonary fibrosis is still largely unknown. In animal model of pulmonary fibrosis, we used HE staining, western blotting assay and Real-time PCR assay to analyze the effects of rapamycin on the PQ-induced epithelial mesenchymal transition (EMT). We found that PQ induced the pulmonary fibrosis using HE staining and Masson's staining, and up-regulated the activity of HYP and the mRNA expressions of Collagen I and III (COL-1and COL-3) in pulmonary tissues. We also found that rapamycin down-regulated the mesenchymal cell marker Vimentin and up-regulated the epithelial cell marker E-cadherin both in mRNA and protein levels compared with PQ group. And the EMT associated transcription factor Snail was decreased by rapamycin treatment compared with PQ group. And PQ decreased the Nrf2 expression both in mRNA and protein levels, and rapamycin inhibited these effects of PQ. SFN, a activator of Nrf2, could inhibit the EMT and the expression of Snail. And knockdowon of Nrf2 could abolish the inhibitory effects of rapamycin of PQ-induced EMT. In conclusion, rapamycin protects against paraquat-induced pulmonary fibrosis by activation of Nrf2 signaling pathway.

IL-27 inhibits the TGF-ß1-induced epithelial-mesenchymal transition in alveolar epithelial cells.

BACKGROUND: IL-27 is a multifunctional cytokine that has both pro-inflammatory and anti-inflammatory functions. Although IL-27 has been shown to potently inhibit lung fibrosis, the detailed mechanism of IL-27 in this process is poorly understood. Epithelial-mesenchymal transition (EMT) is one of the key mechanisms involved in pulmonary fibrosis. We assessed the effects of IL-27 on TGF-ß1-induced EMT in alveolar epithelial cells. METHODS: A549 cells (a human AEC cell line) were incubated with TGF-ß1, IL-27, or both TGF-ß1 and IL-27, and changes in E-cadherin, ß-catenin, vimentin and a-SMA levels were measured using real-time PCR, western blotting and fluorescence microscopy. The related proteins in the JAK/STAT and TGF-ß/Smad signalling pathways were examined by western blot. RESULTS: IL-27 increased the expression of epithelial phenotypic markers, including E-cadherin and ß-catenin, and inhibited mesenchymal phenotypic markers, including vimentin and a-SMA in A549 cells. Moreover, TGF-ß1-induced EMT was attenuated by IL-27. Furthermore, we found that TGF-ß1 activated the phosphorylation of JAK1, STAT1, STAT3, STAT5, Smad1, Smad3 and Smad5, and IL-27 partially inhibited these changes in this process. When cells were treated with the STAT3 specific inhibitor wp1006 and the Smad3 specific inhibitor SIS3, the inhibition of EMT by IL-27 was significantly strengthened. CONCLUSION: Our results suggest that IL-27 attenuates epithelial-mesenchymal transition in alveolar epithelial cells in the absence or presence of TGF-ß1 through the JAK/STAT and TGF-ß/Smad signalling pathways.

4D Printing Technology Based on Magnetic Intelligent Materials: Materials, Processing Processes, and Application.

4D printing technology refers to the manufacturing of products using 3D printing techniques that are capable of changing shape or structure in response to external stimuli. Compared with traditional 3D printing, the additional dimension is manifested in the time dimension. Facilitated by the advancement of magnetic smart materials and 3D printing technology, magnetically controlled 4D printing technology has a wide range of application prospects in many fields such as medical treatment, electronic flexible devices, and industrial manufacturing. Magnetically controlled 4D printing technology is a new scientific research field in the 21st century, which includes but is not limited to the following disciplines: mechanics, materials, dynamics, physics, thermodynamics, and electromagnetism. It involves many fields and needs to be summarized systematically. First, this article introduces various magnetic intelligent materials, which are suitable for magnetically controlled 4D printing, and discusses their programmability. Second, regarding the printing process, the article introduces how to preset the material distribution as well as the research progress about the optimization of magnetically controlled 4D printing platforms and the distribution of magnetic field profiles. Third, the article also makes a brief introduction to the applications of magnetically controlled 4D printing technology in medical, electronic flexible devices, and industrial manufacturing fields.

Analysis of UGT1A1 genotype-phenotype correlation in Chinese patients with gilbert and crigler-Najjar II syndrome.

The spectrum of UDP-glucuronosyltransferase (UGT1A1) variants, which are associated with Gilbert syndrome (GS) and Crigler-Najjar syndrome (CNS-II), has been reported in Chinese and western countries. However, the genotype-phenotype correlation of the individual UGT1A1 variants in GS and CNS-II remains to be clarified. To explore the UGT1A1 variant pattern and genotype-phenotype correlations, we enrolled 310 Chinese patients, including 232 patients with GS and 78 with CNS-II. Peripheral blood samples were collected for screening variants in the gene UGT1A1 by a polymerase chain reaction and Sanger sequencing. The correlation between different UGT1A1 variants and clinical phenotypes was analyzed. A total of 21 UGT1A1 variants were identified, including nine novel variants, and constituted 42 UGT1A1 genotypes in the GS and CNS-II patients. The most common UGT1A1 variants were A (TA)7TAA, p.G71R, p.Y486D, p.P364L, and p.P229Q, which were different from western countries. The p.Y486D variant had higher minor allele frequency in CNS-II than in GS whereas the A (TA)7TAA variant had higher minor allele frequency in GS than in CNS-II. The serum total bilirubin and triglyceride had significant differences among 14 recurrent genotypes of UGT1A1, in which the serum total bilirubin in patients with compound p.Y486D (homozygous)/p.G71R variant was significantly higher compared with homozygous A (TA)7TAA, homozygous p.G71R, compound heterozygous A (TA)7TAA/p.G71R and A (TA)7TAA/p.P364L, and combined heterozygous A (TA)7TAA/p.G71R/p.P229Q, while the serum triglyceride in patients with combined A (TA)7TAA (homozygous)/p.P229Q variant was significantly higher compared with compound heterozygous A (TA)7TAA/p.G71R, single heterozygous A (TA)7TAA, single heterozygous p.G71R, and homozygous A (TA)7TAA. The spectrum of UGT1A1 genotypes in Chinese patients was distinct from western countries. There were differential levels of serum total bilirubin and triglyceride in patients with recurrent genotypes of UGT1A1.

CST3 alleviates bilirubin-induced neurocytes' damage by promoting autophagy.

High concentrations of unconjugated bilirubin (UCB) have toxic effects. The aim of our study was to find a way to elevate UCB tolerance or inhibit its toxicity in neurocytes. It has been reported that cystatin C (CST3) concentrations have a significant positive correlation with total bilirubin (TB) levels and a negative correlation with albumin levels. In addition, CST3 can directly bind UCB, decrease human umbilical vein endothelial cells' permeability, improve blood-brain barrier integrity after ischemic brain injury in mice, and induce autophagy. We hypothesized that CST3 could increase the solubility of UCB, decrease permeability of neurocytes, induce autophagy of neurocytes, and alleviate bilirubin-induced damage. To verify our hypothesis, we measured TB and conjugated bilirubin levels, and the permeability and autophagy of neurocytes treated with UCB and CST3. Our findings suggest that CST3 can protect against UCB-induced damage in neurocytes and that autophagy played an important role in this process.

A Time-Domain Signal Processing Algorithm for Data-Driven Drive-by Inspection Methods: An Experimental Study.

Constructional material deterioration and member damage can cause changes in the dynamic characteristics of bridge structures, and such changes can be tracked in the responses of passing vehicles via the vehicle-bridge interaction (VBI). Though data-driven methods have shown promising results in damage inspection for drive-by methods, there is still much room for improvement in their performance. Given this background, this paper proposes a novel time-domain signal processing algorithm for the raw vehicle acceleration data of data-driven drive-by inspection methods. To achieve the best data processing performance, an optimizing strategy is designed to automatically search for the optimal parameters, tuning the algorithm. The proposed method intentionally overcomes the difficulties in the application of drive-by methods, such as measurement noise, speed variance, and enormous data volumes. Meanwhile, the use of this method can greatly improve the accuracy and efficiency of Machine Learning (ML) models in vehicle-based damage detection. It consists of a filtering process to denoise the data, a pooling process to reduce data redundancy, and an optimizing procedure to maximize algorithm performance. A dataset is obtained to validate the proposed algorithm through laboratory experiments with a scale truck model and a steel beam. The results show that, compared to using raw data, the present algorithm can increase the average accuracy by 12.2-15.0%, and the average efficiency by 35.7-96.7% for different damaged cases and ML models. Additionally, the functions of filtering and pooling operations, the influence of window function parameters, as well as the performance of different sensor locations, are also investigated in the paper. The goal is to present a signal processing algorithm for data-driven drive-by inspection methods to improve their detection performance of bridge damage caused by material deterioration or structural change.

Investigation of Frequency-Domain Dimension Reduction for A2M-Based Bridge Damage Detection Using Accelerations of Moving Vehicles.

Recent decades have witnessed a rise in interest in bridge health monitoring utilizing the vibrations of passing vehicles. However, existing studies commonly rely on constant speeds or tuning vehicular parameters, making their methods challenging to be used in practical engineering applications. Additionally, recent studies on the data-driven approach usually need labeled data for damage scenarios. Still, getting these labels in engineering is difficult or even impractical because the bridge is typically in a healthy state. This paper proposes a novel, damaged-label-free, machine-learning-based, indirect bridge-health monitoring method named the assumption accuracy method (A2M). Initially, the raw frequency responses of the vehicle are employed to train a classifier, and K-folder cross-validation accuracy scores are then used to calculate a threshold to specify the bridge's health state. Compared to merely focusing on low-band frequency responses (0-50 Hz), utilizing full-band vehicle responses can significantly improve the accuracy, meaning that the bridge's dynamic information exists in the higher frequency ranges and can contribute to detecting bridge damage. However, raw frequency responses are generally in a high-dimensional space, and the number of features is much greater than that of samples. To represent the frequency responses via latent representations in a low-dimension space, appropriate dimension-reduction techniques are therefore, needed. It was found that principal component analysis (PCA) and Mel-frequency cepstral coefficients (MFCCs) are suitable for the aforementioned issue, and MFCCs are more damage-sensitive. When the bridge is in a healthy condition, the accuracy values obtained using MFCCs are primarily dispersed around 0.5, but following the occurrence of damage, they increased significantly to 0.89-1.0 in this study.

Bionic Structure Inspired by Tree Frogs to Enhance Damping Performance.

Magnetic fluid shock absorbers (MFSAs) have been successfully utilized to eliminate microvibrations of flexible spacecraft structures. The method of enhancing the damping efficiency of MFSAs has always been a critical issue. To address this, we drew inspiration from the tree frog's toe pads, which exhibit strong friction due to their unique surface structure. Using 3D printing, we integrated bionic textures copied from tree frog's toe pad surfaces onto MFSAs, which is the first time to combine bionic design and MFSAs. Additionally, this is also the first time that surface textures have been applied to MFSAs. However, we also had to consider practical engineering applications and manufacturing convenience, so we modified the shape of bionic textures. To do so, we used an edge extraction algorithm for image processing and obtained recognition results. After thorough consideration, we chose hexagon as the shape of surface textures instead of bionic textures. For theoretical analysis, a magnetic field-flow field coupling dynamic model for MFSAs was built for the first time to simulate the magnetic fluid (MF) flow in one oscillation cycle. Using this model, the flow rate contours of the MF were obtained. It was observed that textures cause vortexes to form in the MF layer, which produced an additional velocity field. This increased the shear rate, ultimately leading to an increase in flow resistance. Finally, we conducted vibration reduction experiments and estimated damping characteristics of the proposed MFSAs to prove the effectiveness of both bionic texture and hexagon surface textures. Fortunately, we concluded that hexagon surface textures not only improve the damping efficiency of MFSAs but also require less MF mass.

Targeted Energy Metabolomics Combined with Spatial Metabolomics Study on the Efficacy of Guhong Injection Against Cerebral Ischemia Reperfusion.

Optimizing the metabolic phenotype to improve cerebral function is critical for treatment of cerebral ischemia-reperfusion (I/R) injury. Guhong injection (GHI), which comprised safflower extract and aceglutamide, is widely prescribed in Chinese medicine for the treatment of cerebrovascular diseases. In this study, a combination of LC-QQQ-MS and MALDI-MSI were utilized to explore tissue-specific metabolic alterations in the brain of I/R, as well as to evaluate the therapeutic effect of GHI. Pharmacological evaluation demonstrated that GHI can significantly improve infarction rate, neurological deficit, cerebral blood flow, and neuronal damage in I/R rats. Based on LC-QQQ-MS, 23 energy metabolites were found to be significantly altered in the I/R group compared to the sham group (P < 0.05). After GHI treatment, 12 metabolites, including G6P, TPP, NAD, citrate, succinate, malate, ATP, GTP, GDP, ADP, NADP, and FMN showed a significant tendency of returning to baseline values (P < 0.05). Based on MALDI-MSI, 4 metabolites in glycolysis and TCA, 4 metabolites in nucleic acid metabolism, 4 amino acid metabolites, and 6 metabolites were discovered and compared between the different groups in the four special regions of cortex, hippocampus, hypothalamus, and striatum. Parts of these were found to have significant changes after I/R in the special brain region, and were regulated by GHI. The study provides comprehensive and detailed information for specific metabolic reprogramming of brain tissue in rats with I/R, and the therapeutic effect of GHI. Schema describing the discovery strategies of integrated LC-MS and MALDI-MSI to identify cerebral ischemia reperfusion metabolic reprogramming and GHI therapeutic effects.