Crashworthiness Study of Functional Gradient Lattice-Reinforced Thin-Walled Tubes under Impact Loading.

Creating lightweight and impact-resistant box structures has been an enduring pursuit among researchers. A new energy-absorbing structure consisting of a bionic gradient lattice-enhanced thin-walled tube is presented in this article. The gradient lattice and thin-walled tube were prepared using selective laser melting (SLM) and wire-cutting techniques, respectively. To analyze the effects of gradient pattern, mass ratio, diameter range and impact speed on structural crashworthiness, low-speed impact at 4 m/s and finite element simulation experiments were conducted. The study demonstrates that the design of inward radial gradient lattice-reinforced thin-walled tubes can effectively enhance structure's energy-absorption efficiency and provide a more stable mode of deformation. It also shows a 17.44% specific energy-absorption advantage over the uniformly lattice-reinforced thin-walled tubes, with no significant overall gain in peak crushing force. A complex scale evaluation method was used to determine the optimum structure and the structure type with the best crashworthiness was found to be a gradient lattice-filled tube with a thickness of 0.9 mm and a slope index of 10. The gradient lattice-reinforced thin-walled tube suggested in this investigation offers guidance for designing a more efficient thin-walled energy-absorption structure.

Low dose phosphorus supplementation is conducive to remediation of heavily petroleum-contaminated soil-From the perspective of hydrocarbon removal and ecotoxicity risk control.

Biostimulation by supplementing of nitrogen and phosphorus nutrients is a common strategy for remediation of petroleum-polluted soils. However, the dosage influence of exogenous nitrogen or phosphorus on petroleum hydrocarbon removal and soil ecotoxicity and microbial function remain unclear. In this study, we compared the efficiencies of hydrocarbon degradation and ecotoxicity control by experiment conducted over addition of inorganic nitrogen or phosphorus at C/N ratio of 100/10, C/N/P ratio of 100/10/1, and C/P ratio of 100/1 in a heavily petroleum-contaminated loessal soil with 12,320 mg/kg of total petroleum hydrocarbon (TPH) content. A 90-day incubation study revealed that low-dose of phosphorus addition with the C/P ratio of 100/1 promoted hydrocarbon degradation and reduced soil ecotoxicity. Microbial community composition analysis suggested that phosphorus addition enriched hydrocarbon degrader Gordonia and Mycolicibacterium genus. The key enzymes EC 5.3.3.8, EC 6.2.1.20 and EC 6.4.1.1 which referred to degradation of long-chain hydrocarbons, unsaturated fatty acids and pyruvate metabolism were abundance by phosphorus supplementation. While nitrogen addition at C/N ratio of 100/10 or C/N/P ratio of 100/10/1 inhibited hydrocarbon degradation and exacerbated soil ecotoxicity due to promoting denitrification and coupling reactions with hydrocarbons. Our results suggested that low-dose phosphorus addition served as a favorable strategy to promote crude oil remediation and ecotoxicity risk control in heavily petroleum-contaminated soil. Hence, the application of suitable doses of exogenous biostimulants is an efficient approach to restore the ecological functions of organically contaminated soils.

Surveillance of tick-borne bacteria infection in ticks and forestry populations in Inner Mongolia, China.

Ticks are one of the most important vectors that can transmit pathogens to animals and human beings. This study investigated the dominant tick-borne bacteria carried by ticks and tick-borne infections in forestry populations in Arxan, Inner Mongolia, China. Ticks were collected by flagging from May 2020 to May 2021, and blood samples were collected from individuals at high risk of acquiring tick-borne diseases from March 2022 to August 2023. The pooled DNA samples of ticks were analyzed to reveal the presence of tick-borne bacteria using high-throughput sequencing of the 16S rDNA V3-V4 region, and species-specific polymerase chain reaction (PCR) related to sequencing was performed to confirm the presence of pathogenic bacteria in individual ticks and human blood samples. All sera samples were examined for anti-SFGR using ELISA and anti-B. burgdorferi using IFA and WB. A total of 295 ticks (282 Ixodes persulcatus and 13 Dermacentor silvarum) and 245 human blood samples were collected. Rickettsia, Anaplasma, Borrelia miyamotoi, and Coxiella endosymbiont were identified in I. persulcatus by high-throughput sequencing, while Candidatus R. tarasevichiae (89.00%, 89/100), B. garinii (17.00%, 17/100), B. afzelii (7.00%, 7/100), and B. miyamotoi (7.00%, 7/100) were detected in I. persulcatus, as well the dual co-infection with Candidatus R. tarasevichiae and B. garinii were detected in 13.00% (13/100) of I. persulcatus. Of the 245 individuals, B. garinii (4.90%, 12/245), R. slovaca (0.82%, 2/245), and C. burnetii (0.41%, 1/245) were detected by PCR, and the sequences of the target genes of B. garinii detected in humans were identical to those detected in I. persulcatus. The seroprevalence of anti-SFGR and anti-B. burgdorferi was 5.71% and 13.47%, respectively. This study demonstrated that Candidatus R. tarasevichiae and B. garinii were the dominant tick-borne bacteria in I. persulcatus from Arxan, and that dual co-infection with Candidatus R. tarasevichiae and B. garinii was frequent. This is the first time that B. miyamotoi has been identified in ticks from Arxan and R. solvaca has been detected in humans from Inner Mongolia. More importantly, this study demonstrated the transmission of B. garinii from ticks to humans in Arxan, suggesting that long-term monitoring of tick-borne pathogens in ticks and humans is important for the prevention and control of tick-borne diseases.

TP53R175H mutation promotes breast cancer cell proliferation through CORO1A-P38 MAPK pathway regulation.

Breast cancer is the most commonly diagnosed cancer in women. Among all types, triple-negative breast cancer is particularly challenging to cure because of its high recurrence rates and invasive and metastatic capacity. Although numerous studies have explored the role of TP53 mutations in cancer, there is a dearth of research regarding the correlation between TP53 mutations and breast cancer cell proliferation. In this study, our aim was to examine the impact of TP53 mutations on the prognosis of patients with breast cancer bioinformatics techniques. To detect cell proliferation, a CCK8 assay was performed, and western blotting was used to identify the expression of p53, p38, and p-p38 proteins. Cellular mRNA sequencing was used to screen target genes of TP53 mutations, and molecular docking was performed to identify the drugs that could hinder the proliferation of breast cancer cells.The results showed that the TP53 mutation rate is higher in patients with triple-negative breast cancer than non-triple-negative breast cancer, and those with TP53 mutations tended to have a poorer prognosis than those without. Patients with R175H site mutations also had shorter survival times than those without. Cytological experiments revealed that the TP53R175H mutation increases the rate of breast cancer cell proliferation. In conjunction with this, CORO1A was found to be a downstream target of TP53 mutations, and it was determined to promote breast cancer cell proliferation. Moreover, CORO1A overexpression resulted in the downregulation of p-p38 levels. Molecular docking studies further revealed that tea polyphenols can inhibit breast cancer proliferation by binding to p53.

Unveiling the Emergence and Genetic Diversity of OXA-48-like Carbapenemase Variants in Shewanella xiamenensis.

An increase in the carbapenem-hydrolyzing capacity of class D ß-lactamase has been observed in strains of multiple species, posing a significant challenge to the control of antibiotic resistance. In this study, we aimed to investigate the genetic diversity and phylogenetic characteristics of new blaOXA-48-like variants derived from Shewanella xiamenensis. Three ertapenem-non-susceptible S. xiamenensis strains were identified, one isolated from the blood sample of an inpatient, the other two isolated from the aquatic environment. Phenotypic characterization confirmed that the strains were carbapenemase producers and exhibited antimicrobial resistance patterns to ertapenem, with some showing lower susceptibility to imipenem, chloramphenicol, ciprofloxacin, and tetracycline. No significant resistance to cephalosporins was observed. Sequence analysis revealed that one strain harbored blaOXA-181 and the other two strains harbored blaOXA-48-like genes, with open reading frame (ORF) similarities with blaOXA-48 ranging from 98.49% to 99.62%. The two novel blaOXA-48-like genes, named blaOXA-1038 and blaOXA-1039, respectively, were cloned and expressed in E. coli. The three OXA-48-like enzymes demonstrated significant hydrolysis activity against meropenem, and the classical ß-lactamase inhibitor had no significant inhibitory effect. In conclusion, this study demonstrated the diversity of the blaOXA gene and highlighted the emergence of novel OXA carbapenemases in S. xiamenensis. Further attention to S. xiamenensis and OXA carbapenemases is recommended for the effective prevention and control of antibiotic-resistant bacteria.

Molecular characteristics and antibiotic resistance mechanisms of clindamycin-resistant Streptococcus agalactiae isolates in China.

Streptococcus agalactiae (Group B Streptococcus, GBS) is a major cause of neonatal infections with high morbidity and mortality, and clindamycin is the main antibiotic used to treat GBS infections in patients allergic to penicillin. We aimed to analyse the antibiotic sensitivity, sequence types, serotypes, virulence factors, and antibiotic resistance mechanisms of clinically isolated clindamycin-resistant S. agalactiae and provide basic data for the treatment, prevention, and control of clinical infection of S. agalactiae. A total of 110 strains of clindamycin-resistant S. agalactiae were collected from two tertiary hospitals in Hebei, China. We performed antibiotic sensitivity tests for 11 antibiotics on these strains and whole-genome sequencing analysis. All the strains were susceptible to penicillin, ampicillin, linezolid, vancomycin, tigecycline, and quinupristin-dalfopristin. Resistance to erythromycin, levofloxacin, tetracycline, and chloramphenicol were also observed. Genome sequence analysis revealed that all strains belonged to 12 sequence types (STs) related to six cloning complexes (CCs), namely CC10, CC19, CC23, CC651, CC1, and CC17. Five serotypes were identified, including IA, IB, II, III, and V. The most prominent resistance genes were mreA (100%) and ermB (81.8%). Furthermore, cfb, cylE, pavA and the gene cluster related to the pili were 100% present in all strains, followed by lmb (95.5%) and srr1 (67.2%). This study found that clindamycin-resistant S. agalactiae showed polymorphisms in molecular types and serotypes. Furthermore, multiple virulence factor genes have been identified in their genomes.

Crashworthiness Study of 3D Printed Lattice Reinforced Thin-Walled Tube Hybrid Structures.

Based on the advantages of thin-walled tubes and lattice structures in energy absorption and improved crashworthiness, a hybrid structure of lattice-reinforced thin-walled tubes with different cross-sectional cell numbers and gradient densities was constructed, and a high crashworthiness absorber with adjustable energy absorption was proposed. The experimental and finite element characterization of the impact resistance of uniform density and gradient density hybrid tubes with different lattice arrangements to withstand axial compression was carried out to investigate the interaction mechanism between the lattice packing and the metal shell, and the energy absorption of the hybrid structure was increased by 43.40% relative to the sum of its individual components. The effect of transverse cell number configuration and gradient configuration on the impact resistance of the hybrid structure was investigated, and the results showed that the hybrid structure showed higher energy absorption than the empty tube, and the best specific energy absorption was increased by 83.02%; the transverse cell number configuration had a greater effect on the specific energy absorption of the hybrid structure with uniform density, and the maximum specific energy absorption of the hybrid structure with different configurations was increased by 48.21%. The gradient density configuration had a significant effect on the peak crushing force of the gradient structure. In addition, the effects of wall thickness, density and gradient configuration on energy absorption were quantitatively analyzed. This study provides a new idea to optimize the impact resistance of lattice-structure-filled thin-walled square tube hybrid structures under compressive loading through a combination of experiments and numerical simulations.

Corrigendum: Current insights into the regulation of programmed cell death by TP53 mutation in cancer.

[This corrects the article DOI: 10.3389/fonc.2022.1023427.].

Current insights into the regulation of programmed cell death by TP53 mutation in cancer.

Gene mutation is a complicated process that influences the onset and progression of cancer, and the most prevalent mutation involves the TP53 gene. One of the ways in which the body maintains homeostasis is programmed cell death, which includes apoptosis, autophagic cell death, pyroptosis, ferroptosis, NETosis, and the more recently identified process of cuprotosis. Evasion of these cell deaths is a hallmark of cancer cells, and our elucidation of the way these cells die helps us better understands the mechanisms by which cancer arises and provides us with more ways to treat it.Studies have shown that programmed cell death requires wild-type p53 protein and that mutations of TP53 can affect these modes of programmed cell death. For example, mutant p53 promotes iron-dependent cell death in ferroptosis and inhibits apoptotic and autophagic cell death. It is clear that TP53 mutations act on more than one pathway to death, and these pathways to death do not operate in isolation. They interact with each other and together determine cell death. This review focuses on the mechanisms via which TP53 mutation affects programmed cell death. Clinical investigations of TP53 mutation and the potential for targeted pharmacological agents that can be used to treat cancer are discussed.

Assessment of bioremediation potential of petroleum-contaminated soils from the shanbei oilfield of China revealed by qPCR and high throughput sequencing.

With the crude oil exploration activities in the Shanbei oilfield of China, the risk of soil contamination with crude oil spills has become a major concern. This study aimed at assessing the bioremediation potential of the petroleum polluted soils by investigating the expression of key functional genes decoding alkane and aromatic component degradation using an array of primers and real-time quantitative PCR (qPCR), and the functional microbiomes were determined using a combination of substrate-induced metabolic responses and high throughput sequencing. The results showed that the species that were more inclined to degrade aliphatic fraction of crude oil included Acinetobacter, Stenotrophomonas, Neorhizobium and Olivebacter. And Pseudomonas genus was a highly specific keystone species with the potential to degrade PAH fraction. Both aliphatic and PAH-degrading genes were upregulated when the soil petroleum contents were less than 10,000 mg/kg but downregulated when the oil contents were over 10,000 mg/kg. Bioremediation potential could be feasible for medium pollution with petroleum contents of less than 10,000 mg/kg. Optimization of the niche of Acinetobacter, Stenotrophomonas, Pseudomonas, Neorhizobium and Olivebacter species was beneficial to the biodegradation of refractory hydrocarbon components in the Shanbei plateau oilfield.

Compression Deformation Prediction of Chiral Metamaterials: A Compression-Shear Coupling Model.

A category of metamaterials consisting of chiral cytosolic elements assembled periodically, in which the introduction of a rotatable annular structure gives metamaterials the ability to deform in compression-shear, has been a focus of research in recent years. In this paper, a compression-shear coupling model is developed to predict the compressive deformation behaviour of chiral metamaterials. This behaviour will be analysed by coupling the rotation of the annular node and the bending characteristics of ligament beam, which are obtained as a function of the length of ligament beam and the angle of rotation at the end of the beam. The shape function of the ligament beam under large deformation is obtained based on the elliptic integral theory; the function characterises the potential relationship between key parameters such as displacement and rotation angle at any point on the ligament beam. By simulating the deformation of cells under uniaxial compression, the reasonableness of the large deformation model of the ligament beam is verified. On this basis, a chiral cell-compression mechanical model considering the ductile deformation of the annular node is established. The compression-shear deformation of two-dimensional planar chiral metamaterials and three-dimensional cylindrical-shell chiral metamaterials was predicted; the offset displacements and torsion angles agreed with the experimental and finite element simulation results with an error of less than 10%. The developed compression-shear coupling model provides a theoretical basis for the design of chiral metamaterials, which meet the need for the precise control of shapes and properties.

Effect of petroleum hydrocarbon pollution levels on the soil microecosystem and ecological function.

Petroleum hydrocarbon pollution is a global problem. However, the effects of different petroleum pollution levels on soil microbial communities and ecological functions are still not clear. In this study, we analyzed the changes in microbial community structures and carbon and nitrogen transformation functions in oil-contaminated soils at different concentrations by chemical analysis, high-throughput sequencing techniques, cooccurrence networks, and KEGG database comparison functional gene annotation. The results showed that heavy petroleum concentrations (petroleum concentrations greater than 20,000 mg kg-1) significantly decreased soil microbial diversity (p = 0.01), soil microbiome network complexity, species coexistence patterns, and prokaryotic carbon and nitrogen fixation genes. In medium petroleum contamination (petroleum concentrations of between 4000 mg kg-1 and 20,000 mg kg-1), microbial diversity (p > 0.05) and carbon and nitrogen transformation genes showed no evident change but promoted species coexistence patterns. Heavy petroleum contamination increased the Proteobacteria phylum abundance by 3.91%-57.01%, while medium petroleum contamination increased the Actinobacteria phylum abundance by 1.69%-0.26%. The results suggested that petroleum concentrations played a significant role in shifting soil microbial community structures, ecological functions, and species diversities.

Mechanical Properties of Cemented Particulate Composite: A 3D Micromechanical Model.

Cemented particulate composite is a kind of composite material with high strength, high energy absorption, and multifunctional characteristics, which is widely used in engineering practice. The calculation of the mechanical properties of granular composites based on theoretical methods has always been a topic of discussion. A micromechanical model with a three-dimensional rigid beam-spring network (3D-RBSN) is proposed here. The stiffness matrix of the model was calculated theoretically. The model was applied to the analysis of the mechanical properties of composites material with glass beads and epoxy resin. The results indicate that the 3D-RBSN model can effectively predict the mechanical properties of composite materials, such as Young's modulus and Poisson's ratio. Furthermore, the damage evolution process of cemented particulate composite with initial defects was analyzed based on the 3D-RBSN model.

HPLC-QTOF/MS-based metabolomics to explore the molecular mechanisms of Yiqi Fumai Lyophilized Injection in heart failure mice.

Chronic heart failure is a common and fatal disease triggered by loss of normal cardiac function. Yiqi Fumai Lyophilized Injection is widely used in the treatment of cardiovascular diseases, especially chronic heart failure. In this study, a model of chronic heart failure in mice was established with permanent coronary artery ligation followed by Yiqi Fumai Lyophilized Injection intervention for 14 days. Then, the endogenous metabolites of mice plasma and urine samples were screened through nontargeted metabolomics techniques. The results indicated that Yiqi Fumai Lyophilized Injection treatment changed the metabolic pattern of chronic heart failure and regulated valine, leucine, and isoleucine biosynthesis, taurine and hypotaurine metabolism, histidine metabolism and arginine biosynthesis, etc. Finally, the cardioprotective mechanism of Yiqi Fumai Lyophilized Injection was further verified in the mouse model of chronic heart failure and angiotensin II-induced cardiac fibroblasts based on metabolomics. The results showed that Yiqi Fumai Lyophilized Injection could inhibit myocardial fibrosis to improve chronic heart failure. This study firstly elucidated the metabolic network and pathways regulated by Yiqi Fumai Lyophilized Injection, which might facilitate the realization of the clinically accurate application of Yiqi Fumai Lyophilized Injection in the treatment of chronic heart failure.

Oxoeicosanoid receptor inhibition alleviates acute myocardial infarction through activation of BCAT1.

5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is an arachidonic acid metabolite produced along with leukotrienes via the 5-lipoxygenase pathway. Metabolomics studies have shown that 5-oxo-ETE level is elevated in the serum in acute myocardial infarction (AMI). The actions of 5-oxo-ETE are mediated by the highly selective oxoeicosanoid receptor (OXE-R). Moreover, increased OXE-R content was verified in AMI patients and mice. However, the precise role of OXE-R in AMI is unclear. In the present study, we demonstrate that 5-oxo-ETE triggered myocardial injury in mice. Pathway enrichment analysis identified branched chain amino acid transaminase 1/2 (BCAT1/2) as potential mediators of this effect. Western blot and immunohistochemical analyses showed that BCAT1/BCAT2 expression was significantly reduced by AMI in vitro and in vivo, while pharmacologic inhibition of BCAT1/BCAT2 accelerated myocardial injury. Conversely, heart-specific overexpression of BCAT1/BCAT2 in mice protected against ischemic myocardial injury. Treatment with the selective OXE-R inhibitor Gue1654 alleviated coronary artery ligation-induced ischemic myocardial injury in mice and oxygen/glucose deprivation-induced injury in cardiomyocytes through activation of BCAT1, while inhibiting OXE-R suppressed protein kinase C-ε (PKC-ε)/nuclear factor κB (NF-κB) signaling and cardiomyocyte apoptosis. Overall, our study confirmed a novel target OXE-R for the treatment of AMI based on metabolomics, and targeting OXE-R may represent unrecognized therapeutic intervention for cardiovascular diseases through activation of BCAT1.

Mechanical and electronic properties of van der Waals layered hcp PdH2.

Mechanical and electronic properties of palladium dihydrides (PdH2) as a function of pressure were studied by ab initio calculations based on density functional theory (DFT). The ab initio random structure searching technique was employed for screening potential PdH2 crystal structures under high pressure. A hexagonal close packed (hcp) phase of PdH2 with space group P63mc was reported. The structure geometry and elastic constants were calculated as a function of pressure. It was found that H atoms are in the interstitial position of Pd atoms layer at 0 GPa. There is an electronic topology transition of hcp PdH2 at 15 GPa. When pressure exceeds above 15 GPa, one hydrogen atom occupies the tetrahedral site and another hydrogen atom locates in the interstitial position. When the c/a ratio is between 1.765 to 1.875, the hcp PdH2 is mechanically stable, and the Pd-H2b bond is the major factor that limits the mechanical stability. The elastic constant C44 is the first one that cannot satisfy the mechanical stability criteria under pressure. The anisotropy parameters are far from 1(one) shows that the hcp PdH2 is a highly anisotropic structure. The electronic structure study indicates that the bonding force between Pd and H atoms along the z-axis direction increases with the increasing pressure. Also, the phonon dispersion study shows that PdH2 is dynamic stability under pressure. The results suggest that hcp PdH2 can be metastable in van der Waals layered structure.

Exploring the protective effects of schizandrol A in acute myocardial ischemia mice by comprehensive metabolomics profiling integrated with molecular mechanism studies.

Schizandrol A (SA) is an bioactive component isolated from the Schisandra chinensis (Turcz.) Baill., which has been used as a remedy to prevent oxidative injury. However, whether the cardioprotective effect of SA is associated with regulating endogenous metabolites remains unclear, thus we performed comprehensive metabolomics profiling in acute myocardial ischemia (AMI) mice following SA treatment. AMI was induced in ICR mice by coronary artery ligation, then SA (6 mg·kg-1·d-1, ip) was administered. SA treatment significantly decreased the infarct size, preserved the cardiac function, and improved the biochemical indicators and cardiac pathological alterations. Moreover, SA (10, 100 M) significantly decreased the apoptotic index in OGD-treated H8c2 cardiomycytes in vitro. By using HPLC-Q-TOF/MS, we conducted metabonomics analysis to screen the significantly changed endogenous metabolites and construct the network in both serum and urine. The results revealed that SA regulated the pathways of glycine, serine and threonine metabolism, lysine biosynthesis, pyrimidine metabolism, arginine and proline metabolism, cysteine and methionine metabolism, valine, leucine and isoleucine biosynthesis under the pathological conditions of AMI. Furthermore, we selected the regulatory enzymes related to heart disease, including ecto-5'-nucleotidase (NT5E), guanidinoacetate N-methyltransferase (GAMT), platelet-derived endothelial cell growth factor (PD-ECGF) and methionine synthase (MTR), for validation. In addition, SA was found to facilitate PI3K/Akt activation and inhibit the expression of NOX2 in AMI mice and OGD-treated H9c2 cells. In conclusion, we have elucidated SA-regulated endogenous metabolic pathways and constructed a regulatory metabolic network map. Furthermore, we have validated the new potential therapeutic targets and underlying molecular mechanisms of SA against AMI, which might provide a reference for its future application in cardiovascular diseases.

Metabolomic profiling of metoprolol-induced cardioprotection in a murine model of acute myocardial ischemia.

Metoprolol (Met) is widely applied in the treatment of myocardial infarction and coronary heart disease in clinic. However, the metabolic network in vivo affected by Met manipulation is still unclear and it's therapeutic molecular mechanisms were remained to be furthered elucidated except ß1 adrenergic receptor. Myocardial infarction (MI) was induced by permanent CAL for 24 h in ICR mice. Myocardial infarct size, biochemical indicators such as creatine kinase (CK), lactate dehydrogenase (LDH), C-reactive Protein (CRP), tumor necrosis factor-α (TNF-α) and cardiac troponin I(cTn-I), cardiac function and myocardial pathological changes were detected to ensure the improvement of Met on MI. Subsequently, the significantly changed endogenous metabolites and the network in both serum and urine were screened and constructed through metabolomics by using HPLC-Q-TOF/MS. Finally, the potential regulatory enzymes that could be the possible new therapeutic targets of Met were selected and validated by western blotting and immunohistochemistry based on the screened differential metabolites and the enrichment analysis. Met effectively reduced the infarct size of myocardial infarction mice, improved the biochemical indicators, and ameliorated the cardiac function and pathological conditions. Our study further found that Met could regulate the pathways of glycine, serine and threonine metabolism, cysteine and methionine metabolism, purine and pyrimidine metabolism under the pathological conditions of MI. Moreover, several regulatory enzymes involved GATM, CSE and NT5E were demonstrated to be regulated by Met. This study constructed the regulatory metabolic network map of Met, elucidated the endogenous metabolic pathway regulated by Met, and validated the new potential therapeutic targets of Met in MI, which might provide a further reference for the clinical application of Met.