An exploratory in-situ dynamic mechanical analysis on the shearing stress-strain mechanism of human plantar soft tissue.

A DMA (dynamic mechanical analysis)-like device based on the principle of classical viscoelasticity testing is invented to investigate the in-situ/in-vivo shear-bearing mechanism of plantar soft tissue. Forty-three volunteers were recruited for the shear-strain test in the longitudinal and transverse directions at five anatomical spots on the plantar surface. Several encouraging observations indicated significant variances among different spots and individuals, implying that the outer forefoot surrounding the second, fifth metatarsal head is a more intensive shear-bearing region on the plantar surface compared to the inner forefoot under the first metatarsal head, and drawing the hypothesis of a significant effect of BMI on the shear-bearing property. The speculations agree with our expectations and other previous research. The feasibility and practical value of this novel approach are substantiated, and these intriguing discoveries provide foundational underpinnings for further in-depth investigations.

A novel in-situ dynamic mechanical analysis for human plantar soft tissue: The device design, definition of characteristics, test protocol, and preliminary results.

The in-situ mechanical characterization of elastomers is not highly regarded due to the existence of a well-established set of sample-based standard tests for research and industry. However, there are certain situations or materials, like biological soft tissue, where an in-situ approach is necessary due to the impossibility of sampling from a living body. We have developed a dynamic mechanical analysis (DMA)-like device to approach in-vivo and in-situ multidimensional stress-strain properties of human plantar soft tissues. This work elucidates the operational mechanism of the novel measurement, with the definition of a new set of moduli, test standardization and protocol. Exploratory results of a volunteer's living plantar, silica rubber samples are presented with well preciseness and consistence as expected.

Biodegradable poly(ethylene glycol-glycerol-itaconate-sebacate) copolyester elastomer with significantly reinforced mechanical properties by in-situ construction of bacterial cellulose interpenetrating network.

To address the concern that biodegradable elastomers are environmental-friendly but usually associated with poor properties for practical utilization, we report a star-crosslinked poly(ethylene glycol-glycerol-itaconate-sebacate) (PEGIS) elastomer synthesized by esterification, polycondensation and UV curing, and reinforced by bacterial cellulose (BC). The interpenetrating network of primary BC backbone and vulcanized elastomer is achieved by the "in-situ secondary network construction" strategy. With the well dispersion of BC without agglomeration, the mechanical properties of PEGIS are significantly enhanced in tensile strength, Young's modulus and elongation at break. The reinforcement strategy is demonstrated to be efficient and offers a route to the development of biodegradable elastomers for a variety of applications in the future.

Effect of Starch Plasticization on Morphological, Mechanical, Crystalline, Thermal, and Optical Behavior of Poly(butylene adipate-co-terephthalate)/Thermoplastic Starch Composite Films.

Starches plasticized with glycerol/citric acid/stearic acid and tributyl 2-acetylcitrate (ATBC), respectively, were processed with poly (butylene adipate-Co-terephthalate (PBAT) via extrusion and a film-blown process. All the composite films were determined for morphology, mechanical, thermal stability, crystalline, and optical properties. Results show that the most improved morphology was in the 30% glycerol plasticized PBAT/thermoplastic starch (TPS) composite films, characterized by the smallest and narrowest distribution of TPS particle sizes and a more uniform dispersion of TPS particles. However, the water absorption of PBAT/TPS composite films plasticized with glycerol surpassed that observed with ATBC as a plasticizer. Mechanical properties indicated insufficient plasticization of the starch crystal structure when using 10% ATBC, 20% ATBC, and 20% glycerol as plasticizers, leading to poor compatibility between PBAT and TPS. This resulted in stress concentration points under external forces, adversely affecting the mechanical properties of the composites. All PBAT/TPS composite films exhibited a negative impact on the initial thermal decomposition temperature compared to PBAT. Additionally, the haze value of PBAT/TPS composite films exceeded 96%, while pure PBAT had a haze value of 47.42%. Films plasticized with 10% ATBC, 20% ATBC, and 20% glycerol displayed lower transmittance values in the visible light region. The increased transmittance of films plasticized with 30% glycerol further demonstrated their superior plasticizing effect compared to other PBAT/TPS composite films. This study provides a simple and feasible method for preparing low-cost PBAT composites, and their extensions are expected to further replace general-purpose plastics in daily applications.

Quantitative patient graph analysis for transient ischemic attack risk factor distribution based on electronic medical records.

A transient ischemic attack (TIA) affects millions of people worldwide. Although TIA risk factors have been identified individually, a systemic quantitative analysis of all health factors relevant to TIA using electronic medical records (EMR) remains lacking. This study employed a data-driven approach, leveraging hospital EMR data to create a TIA patient health factor graph. This graph consisted of 737 TIA and 737 control patient nodes, 740 health factor nodes, and over 33,000 relations between patients and factors. For all health factors in the graph, the connection delta ratios (CDRs) were determined and ranked, generating a quantitative distribution of TIA health factors. A literature review confirmed 56 risk factors in the distribution and unveiled a potential new risk factor "rhinosinusitis" for future validation. Moreover, the patient graph was visualized together with the TIA knowledge graph in the Unified Medical Language System. This integration enables clinicians to access and visualize patient data and international standard knowledge within a unified graph. In conclusion, graph CDR analysis can effectively quantify the distribution of TIA risk factors. The resulting TIA risk factor distribution might be instrumental in developing new risk prediction machine learning models for screening and early detection of TIA.

Study on the intervention effect of Epimedium before and after suet-oil-processed on kidney yang deficiency rats based on intestinal flora and fecal metabolomics.

Epimedium is a Chinese herbal medicine commonly used in clinical practice to reinforce yang. Previous studies have shown that Epimedium fried with suet oil based has the best effect on warming kidney and promoting yang. Evidence suggests a relationship between kidney yang deficiency syndrome (KYDS) and metabolic disorders of the intestinal microflora. However, the specific interaction between KYDS and the intestinal microbiome, as well as the internal regulatory mechanism of the KYDS intestinal microbiome regulated by Epimedium fried with suet oil, remain unclear. The purpose of this study was to investigate the regulatory effects of different processed products of Epimedium on intestinal microflora and metabolites in rats with kidney yang deficiency, and to reveal the processing mechanism of Epimedium fried with suet oil warming kidney and helping yang. 16 S rRNA and LC-MS/MS technology were used to detect fecal samples. Combined with multivariate statistical analysis, differential intestinal flora and metabolites were screened. Then the content of differential bacteria was then quantified using quantitative real-time fluorescence PCR. Furthermore, the correlation between differential bacterial flora and metabolites was analyzed using Spearman's method. The study found that the composition of intestinal flora in rats with kidney yang deficiency changed compared to healthy rats. Epimedium fried with suet oil could increase the levels of beneficial bacteria, while significantly reducing the levels of harmful bacteria. Real-time quantitative PCR results were consistent with 16 S rRNA gene sequencing analysis. Fecal metabolomics revealed that KYDS was associated with 30 different metabolites, involving metabolic pathways steroid hormone biosynthesis etc. Moreover, differential bacteria were closely correlated with potential biomarkers. Epimedium could improve metabolic disorders associated with KYDS by acting on the intestinal flora, with Epimedium fried with suet oil demonstrating the most effective regulatory effect. Its potential mechanism may involve the regulation of abnormal metabolism and the impact on the diversity and structure of the intestinal flora.

Higher-order singularities in phase-tracked electromechanical oscillators.

Singularities ubiquitously exist in different fields and play a pivotal role in probing the fundamental laws of physics and developing highly sensitive sensors. Nevertheless, achieving higher-order (≥3) singularities, which exhibit superior performance, typically necessitates meticulous tuning of multiple (≥3) coupled degrees of freedom or additional introduction of nonlinear potential energies. Here we propose theoretically and confirm using mechanics experiments, the existence of an unexplored cusp singularity in the phase-tracked (PhT) steady states of a pair of coherently coupled mechanical modes without the need for multiple (≥3) coupled modes or nonlinear potential energies. By manipulating the PhT singularities in an electrostatically tunable micromechanical system, we demonstrate an enhanced cubic-root response to frequency perturbations. This study introduces a new phase-tracking method for studying interacting systems and sheds new light on building and engineering advanced singular devices with simple and well-controllable elements, with potential applications in precision metrology, portable nonreciprocal devices, and on-chip mechanical computing.

Light-Assisted "Nano-Neutrophils" with High Drug Loading for Targeted Cancer Therapy.

Background: Nanomedicine presents a promising alternative for cancer treatment owing to its outstanding features. However, the therapeutic outcome is still severely compromised by low tumor targeting, loading efficiency, and non-specific drug release. Methods: Light-assisted "nano-neutrophils (NMPC-NPs)", featuring high drug loading, self-amplified tumor targeting, and light-triggered specific drug release, were developed. NMPC-NPs were composed of neutrophil membrane-camouflaged PLGA nanoparticles (NPs) loaded with a hypoxia-responsive, quinone-modified PTX dimeric prodrug (hQ-PTX2) and photosensitizer (Ce6). Results: hQ-PTX2 significantly enhanced the drug loading of NPs by preventing intermolecular π-π interactions, and neutrophil membrane coating imparted the biological characteristics of neutrophils to NMPC-NPs, thus improving the stability and inflammation-targeting ability of NMPC-NPs. Under light irradiation, extensive NMPC-NPs were recruited to tumor sites based on photodynamic therapy (PDT)-amplified intratumoral inflammatory signals for targeted drug delivery to inflammatory tumors. Besides, PDT could effectively eliminate tumor cells via reactive oxygen species (ROS) generation, while the PDT-aggravated hypoxic environment accelerated hQ-PTX2 degradation to realize the specific release of PTX, thus synergistically combining chemotherapy and PDT to suppress tumor growth and metastasis with minimal adverse effects. Conclusion: This nanoplatform provides a prospective and effective avenue toward enhanced tumor-targeted delivery and synergistic cancer therapy.

Piezoelectric materials for neuroregeneration: a review.

The purpose of nerve regeneration via tissue engineering strategies is to create a microenvironment that mimics natural nerve growth for achieving functional recovery. Biomaterial scaffolds offer a promising option for the clinical treatment of large nerve gaps due to the rapid advancement of materials science and regenerative medicine. The design of biomimetic scaffolds should take into account the inherent properties of the nerve and its growth environment, such as stiffness, topography, adhesion, conductivity, and chemical functionality. Various advanced techniques have been employed to develop suitable scaffolds for nerve repair. Since neuronal cells have electrical activity, the transmission of bioelectrical signals is crucial for the functional recovery of nerves. Therefore, an ideal peripheral nerve scaffold should have electrical activity properties similar to those of natural nerves, in addition to a delicate structure. Piezoelectric materials can convert stress changes into electrical signals that can activate different intracellular signaling pathways critical for cell activity and function, which makes them potentially useful for nerve tissue regeneration. However, a comprehensive review of piezoelectric materials for neuroregeneration is still lacking. Thus, this review systematically summarizes the development of piezoelectric materials and their application in the field of nerve regeneration. First, the electrical signals and natural piezoelectricity phenomenon in various organisms are briefly introduced. Second, the most commonly used piezoelectric materials in neural tissue engineering, including biocompatible piezoelectric polymers, inorganic piezoelectric materials, and natural piezoelectric materials, are classified and discussed. Finally, the challenges and future research directions of piezoelectric materials for application in nerve regeneration are proposed.

Bioinformatic analysis of CHEK1 as a marker of glomerular epithelial cell injury in diabetic nephropathy.

Diabetic nephropathy (DN) is considered to be a kidney disease caused by diabetes. In recent years, the incidence of DN has been on the rise, which is also a major challenge in the treatment and prognosis of the disease. Therefore, the search for new biomarkers of DN is urgent and has important clinical significance for reducing the morbidity and mortality of DN. In this study, two datasets GSE1009 and GSE142153 were selected to extract expression profile-based data from DN glomerular samples, and 238 differentially expressed genes (DEGs) were screened. Then, through enrichment analysis, the biological function of DEGs involved in DN disease was preliminarily explored. Subsequently, the STRING website was used to construct a protein-protein interaction map (PPI) to find 10 key genes (CHEK1, ITGB3, COL4A2, COL4A5, COL4A3, COL4A4, CCNB2, CCNB1, TPX2, KIF11), Which play an important role in the progression of DN disease and are closely related to other genes. CHEK1 was the focus of this study, and the expression level of CHEK1 in glomerular epithelial cell models was verified by qRT-PCR. Our results suggest that CHEK1 is a potential biomarker of the degree of damage to DN glomerular epithelial cells.

Prognosis signature for predicting the survival and immunotherapy response in esophageal carcinoma based on cellular senescence-related genes.

Background: Cellular senescence occurs throughout life and can play beneficial roles in a variety of physiological processes, including embryonic development, tissue repair, and tumor suppression. However, the relationship between cellular senescence-related genes (CSRGs) and immunotherapy in esophageal carcinoma (ECa) remains poorly defined. Methods: The data set used in the analysis was retrieved from TCGA (Research Resource Identifier (RRID): SCR_003193), GEO (RRID: SCR_005012), and CellAge databases. Data processing, statistical analysis, and diagram formation were conducted in R software (RRID: SCR_001905) and GraphPad Prism (RRID: SCR_002798). Based on CSRGs, we used the TCGA database to construct a prognostic signature for ECa and then validated it in the GEO database. The predictive efficiency of the signature was evaluated using receiver operating characteristic (ROC) curves, Cox regression analysis, nomogram, and calibration curves. According to the median risk score derived from CSRGs, patients with ECa were divided into high- and low-risk groups. Immune infiltration and immunotherapy were also analyzed between the two risk groups. Finally, the hub genes of the differences between the two risk groups were identified by the STRING (RRID: SCR_005223) database and Cytoscape (RRID: SCR_003032) software. Results: A six-gene risk signature (DEK, RUNX1, SMARCA4, SREBF1, TERT, and TOP1) was constructed in the TCGA database. Patients in the high-risk group had a worse overall survival (OS) was disclosed by survival analysis. As expected, the signature presented equally prognostic significance in the GSE53624 cohort. Next, the Area Under ROC Curve (AUC=0.854) and multivariate Cox regression analysis (HR=3.381, 2.073-5.514, P<0.001) also proved that the risk signature has a high predictive ability. Furthermore, we can more accurately predict the prognosis of patients with ECa by nomogram constructed by risk score. The result of the TIDE algorithm showed that ECa patients in the high-risk group had a greater possibility of immune escape. At last, a total of ten hub genes (APOA1, MUC5AC, GC, APOA4, AMBP, FABP1, APOA2, SOX2, MUC8, MUC17) between two risk groups with the highest interaction degrees were identified. By further analysis, four hub genes (APOA4, AMBP, FABP1, and APOA2) were related to the survival differences of ECa. Conclusions: Our study reveals comprehensive clues that a novel signature based on CSRGs may provide reliable prognosis prediction and insight into new therapy for patients with ECa.

Integrated metabolome-microbiome analysis investigates the different regulations of Pudilan Xiaoyan oral liquid in young rats with acute pharyngitis compared to adult rats.

BACKGROUND: Pudilan Xiaoyan Oral Liquid (PDL) is a famous traditional Chinese prescription recorded in the Chinese Pharmacopeia, which is widely used to treat inflammatory diseases of the respiratory tract in children and adults. However, the endogenous changes in children and adults with PDL in the treatment of acute pharyngitis remain unclear. PURPOSE: The differential regulatory roles of PDL in endogenous metabolism and gut microbes in young and adult rats were investigated with a view to providing a preclinical data reference for PDL in medication for children. METHODS: An acute pharyngitis model was established, and serum levels of inflammatory factors and histopathology were measured. This study simulated the growth and development of children in young rats and explored the endogenous metabolic characteristics and intestinal microbial composition after the intervention of PDL by using serum metabolomic technique and 16S rRNA high-throughput sequencing technique. RESULTS: The results showed that PDL had therapeutic effects on young and adult rats with acute pharyngitis. Sixteen biomarkers were identified by metabolomics in the serum of young rats and 23 in adult rats. PDL can also affect intestinal microbial diversity and community richness in young and adult rats. Alloprevotella, Allobaculum, Alistipes, Bifidobacterium, and Enterorhabdus were prominent bacteria in young rats. Bacteria from the phylum Firmicutes of the adult rats changed more significantly under the treatment of PDL. In young rats, amino acid metabolism was the primary regulatory mode of PDL, whereas, in adult rats, glycerophospholipid metabolism was studied. CONCLUSION: The regulation of PDL on the serum metabolite group and intestinal microflora in young rats was different from that in adult rats, indicating the necessity of an independent study on children's medication. PDL may also exert therapeutic effects on young and adult rats by regulating gut microbial homeostasis. The results support the clinical application of PDL.

A Novel UV Barrier Poly(lactic acid)/Poly(butylene succinate) Composite Biodegradable Film Enhanced by Cellulose Extracted from Coconut Shell.

Cellulose was extracted from coconut shell powder (CSP) as a renewable biomass resource and utilized as a reinforcing material in poly(lactic acid)/poly(butylene succinate) (PLA/PBS) solvent casting films. The extraction process involved delignification and mercerization of CSP. Microscopic investigation of the extracted microfibers demonstrated a reduction in diameter and a rougher surface characteristic compared to the raw CSP. The cellulose prepared in this study exhibited improved thermal stability and higher crystallinity (54.3%) compared to CSP. The morphology of the cycrofractured surface, thermal analysis, mechanical property, and UV transmittance of films were measured and compared. Agglomeration of 3 wt.% of cellulose was observed in PLA/PBS films. The presence of cellulose higher than 1 wt.% in the PLA/PBS decreased the onset decomposition temperature and maximum decomposition temperature of films. However, the films loading 3 wt.% of cellulose had a higher char formation (5.47%) compared to neat PLA/PBS films. The presence of cellulose promoted the formation of non-uniform crystals, while cellulose had a slightly negative impact on crystallinity due to the disruption of polymer chains at lower cellulose content (0.3, 0.5 wt.%). The mechanical strength of PLA/PBS films decreased as the cellulose content increased. Moreover, PLA/PBS film with 3 wt.% of cellulose appeared to show a 3% and 7.5% decrease in transmittance in UVC (275 nm) and UVA (335 nm) regions compared to neat PLA/PBS films while maintaining a certain transparency.

Multi-scale, multi-level anisotropic silk fibroin/metformin scaffolds for repair of peripheral nerve injury.

Silk fibroin (SF) as a natural polymer has a long history of application in various regenerative medicine fields, but there are still many shortcomings in silk fibroin for using as nerve scaffolds, which limit its clinical application in peripheral nerve regeneration (PNR). In this work, a multi-scale and multi-level metformin (MF)-loaded silk fibroin scaffold with anisotropic micro-nano composite topology was prepared by micromolding electrospinning for accelerating PNR. The scaffolds were characterized for morphology, wettability, mechanical properties, degradability, and drug release, and Schwann cells (SCs) and dorsal root ganglia (DRG) were cultured on the scaffolds to assess their effects on neural cell behavior. Finally, the gene expression differences of neural cells cultured on scaffolds were analyzed by gene sequencing and RT-qPCR to explore the possible signaling pathways and mechanisms. The results showed that the scaffolds had excellent mechanical properties and hydrophilicity, slow degradation rate and drug release rate, which were enough to support the repair of peripheral nerve injury for a long time. In Vitro cell experiments showed that the scaffolds could significantly promote the orientation of SCs and axons extension of DRG. Gene sequencing and RT-qPCR revealed that the scaffolds could up-regulate the expression of genes related to SCs proliferation, adhesion, migration, and myelination. In summary, the scaffolds hold great potential for promoting PNR at the micro/nano multiscale and physical/chemical levels and show promising application for the treatment of peripheral nerve injury in the future.

Multi-Site Attack, Neutrophil Membrane-Camouflaged Nanomedicine with High Drug Loading for Enhanced Cancer Therapy and Metastasis Inhibition.

Background: Advanced breast cancer is a highly metastatic tumor with high mortality. Simultaneous elimination of primary tumor and inhibition of neutrophil-circulation tumor cells (CTCs) cluster formation are urgent issues for cancer therapy. Unfortunately, the drug delivery efficiency to tumors and anti-metastasis efficacy of nanomedicine are far from satisfactory. Methods: To address these problems, we designed a multi-site attack, neutrophil membrane-camouflaged nanoplatform encapsulating hypoxia-responsive dimeric prodrug hQ-MMAE2 (hQNM-PLGA) for enhanced cancer and anti-metastasis therapy. Results: Encouraged by the natural tendency of neutrophils to inflammatory tumor sites, hQNM-PLGA nanoparticles (NPs) could target delivery of drug to tumor, and the acute hypoxic environment of advanced 4T1 breast tumor promoted hQ-MMAE2 degradation to release MMAE, thus eliminating the primary tumor cells to achieve remarkable anticancer efficacy. Alternatively, NM-PLGA NPs inherited the similar adhesion proteins of neutrophils so that NPs could compete with neutrophils to interrupt the formation of neutrophil-CTC clusters, leading to a reduction in extravasation of CTCs and inhibition of tumor metastasis. The in vivo results further revealed that hQNM-PLGA NPs possessed a perfect safety and ability to inhibit tumor growth and spontaneous lung metastasis. Conclusion: This study demonstrates the multi-site attack strategy provides a prospective avenue with the potential to improve anticancer and anti-metastasis therapeutic efficacy.

Effects of insecticidal proteins of Enterobacter cloacae NK on cellular immunity of Galleria mellonella larvae.

Enterobacter cloacae produces insecticidal proteins capable of causing toxicity in pests, but the insecticidal mechanisms of these proteins for insect control remain unclear. To elucidate the mechanisms, the purified insecticidal protein from E. cloacae NK was administered to Galleria mellonella larvae either by intraperitoneal injection or by feeding. The number of hemocytes, apoptosis in immune cells, and polyphenol oxidase (PO) activity of G. mellonella larvae were detected by hemocytometer, Annexin V-FITC/PI, and UV-vis spectrophotometer, respectively. With the extension of the invasion time of NK insecticidal protein, the number of hemocytes in G. mellonella larvae decreased significantly (p < 0.05), whereas the apoptosis rate of hemocytes increased. The activity of PO showed a trend of rising-peak-sharp decline and the melanization reaction was deepened simultaneously. Moreover, the phagocytosis and coating capabilities of hemocytes decreased, and the intraperitoneal injection method was more effective than the feeding method. Taking together, the insecticidal protein of E. cloacae NK inhibits and destroys the cellular immune response of G. mellonella larvae, which suggests an important role in killing the host insect.

Generation, mechanisms, kinetics, and effects of gaseous chlorine dioxide in food preservation.

Food preservation is a critical issue in ensuring food safety and quality. Growing concern around industrial pollution of food and demand for environmentally sustainable food has led to increased interest in developing effective and eco-friendly preservation techniques. Gaseous ClO2 has gained attention for its strong oxidizing properties, high efficacy in microorganism inactivation, and potential for preserving the attributes and nutritional quality of fresh food while avoiding the formation of toxic byproducts or unacceptable levels of residues. However, the widespread use of gaseous ClO2 in the food industry is limited by several challenges. These include large-scale generation, high cost and environmental considerations, a lack of understanding of its mechanism of action, and the need for mathematical models to predict inactivation kinetics. This review aims to provide an overview of the up-to-date research and application of gaseous ClO2 . It covers preparation methods, preservation mechanisms, and kinetic models that predict the sterilizing efficacy of gaseous ClO2 under different conditions. The impacts of gaseous ClO2 on the quality attributes of fresh produce and low-moisture foods, such as seeds, sprouts, and spices, are also summarized. Overall, gaseous ClO2 is a promising preservation approach, and future studies are needed to address the challenges in large-scale generation and environmental considerations and to develop standardized protocols and databases for safe and effective use in the food industry.

A collaborative scheduling model for production and transportation of ready-mixed concrete.

Ready-mixed-concrete (RMC) is an important green and clean building material which is widely used in modern civil engineering. For the large-scale planar foundations of urban public buildings, huge amounts of RMC need to be continuously delivered to the construction site according to strict time windows, which brings the problem of multi-plants collaborative supply. In this paper, considering transportation capacity, initial setting time, and interrupt pumping time, a collaborative scheduling model for production and transportation of RMC with the objective of minimizing the penalty cost of interruption pumping and vehicle waiting time and fuel consumption cost was established. According to the characteristics of the problem, a double chromosome synchronous evolution genetic algorithm was designed. Finally, the model and algorithm proposed in the paper were verified by data experiments. The computing results showed that in two cases of different scenarios, such as ordinary constructions and emergency constructions, the proposed scheduling model can save 18.6 and 24.8% cost respectively. The scheduling model and algorithm proposed in the paper can be applied directly to improve the operational efficiency of RMC supply chain.

Integrating strategies of metabolomics, network pharmacology, and experiment validation to investigate the processing mechanism of Epimedium fried with suet oil to warm kidney and enhance yang.

Introduction: Epimedium, a traditional Chinese medicine (TCM) commonly used in ancient and modern China, is one of the traditional Chinese medicines clinically used to treat kidney yang deficiency syndrome (KYDS). There are differences in the efficacy of Epimedium before and after processing, and the effect of warming the kidney and enhancing yang is significantly enhanced after heating with suet oil. However, the active compounds, corresponding targets, metabolic pathways, and synergistic mechanism of frying Epimedium in suet oil to promote yang, remain unclear. Methods: Herein, a strategy based on comprehensive GC-TOF/MS metabolomics and network pharmacology analysis was used to construct an "active compounds-targets-metabolic pathways" network to identify the active compounds, targets and metabolic pathways involved. Subsequently, the targets in kidney tissue were further validated by real-time quantitative polymerase chain reaction (RT-qPCR). Histopathological analysis with physical and biochemical parameters were performed. Results: Fifteen biomarkers from urine and plasma, involving five known metabolic pathways related to kidney yang deficiency were screened. The network pharmacology results showed 37 active compounds (13 from Epimedium and 24 from suet oil), 159 targets, and 267 pathways with significant correlation. Importantly, integrated metabolomics and network pharmacologic analysis revealed 13 active compounds (nine from Epimedium and four from suet oil), 7 corresponding targets (ALDH2, ARG2, GSTA3, GSTM1, GSTM2, HPGDS, and NOS2), two metabolic pathways (glutathione metabolism, arginine and proline metabolism), and two biomarkers (Ornithine and 5-Oxoproline) associated with improved kidney yang deficiency by Epimedium fried with suet oil. Discussion: These finds may elucidate the underlying mechanism of yang enhancement via kidney warming effects. Our study indicated that the mechanism of action mainly involved oxidative stress and amino acid metabolism. Here, we demonstrated the novel strategies of integrating metabolomics and network pharmacology in exploring of the mechanisms of traditional Chinese medicines.