Electronic coupling of iron-cobalt in Prussian blue towards improved peroxydisulfate activation.

Prussian blue analogs (PBAs) have attracted extensive attention in the field of aqueous organic degradation due to the tremendous potential for peroxydisulfate (PDS) activation. However, the relationship between the d-band center of the catalyst and the activation behavior of PDS remained largely unexplored. Herein, a series of Fe-Co PBAs-based catalysts with different Fe/Co ratios (Fe-Co PBAs-1 = 1: 0.52; Fe-Co PBAs-2 = 1: 1.21, and Fe-Co PBAs-3 = 1: 1.48) have been prepared by a facile hydrothermal procedure and subsequent acid treatment (Fe-Co PBAs-xH). The as-prepared Fe-Co PBAs-xH exhibited superior PDS activation performance and excellent recyclability in the degradation of methylene blue (MB). Density functional theory calculations revealed that the electron-occupied state of the Fe-Co PBAs was shifted to the Fermi level, indicating a strong interaction and easier electron transfer. Moreover, the d-band center of Fe-Co PBAs was upshifted relative to that of Fe PBAs, suggesting easier adsorption of MB and PDS, which was beneficial to enhancing catalytic activation and subsequent dissociation. Radicals such as •OH, 1O2, O2•-, and SO4•- were determined by the radical quenching experiment and electron paramagnetic resonance (EPR) testing in the Fe-Co PBAs-3H/PDS system, and the order of MB degradation by the free active radical is •OH > 1O2 > O2•- > SO4•-. The degradation pathway and potential ecotoxicity of MB and its intermediates were also studied. This work can provide new insights to construct the efficient catalysts for the activation of PDS and the degradation of organic pollutants.

CTPS cytoophidia formation affects cell cycle progression and promotes TSN­induced apoptosis of MKN45 cells.

Cytidine triphosphate synthase (CTPS) forms filamentous structures termed cytoophidia in numerous types of cell. Toosendanin (TSN) is a tetracyclic triterpenoid and induces CTPS to form cytoophidia in MKN45 cells. However, the effects of CTPS cytoophidia on the proliferation and apoptosis of human gastric cancer cells remain poorly understood. In the present study, CTPS­overexpression and R294D­CTPS mutant vectors were generated to assess the effect of CTPS cytoophidia on the proliferation and apoptosis of gastric cancer MKN45 cells. Formation of CTPS cytoophidia significantly inhibited MKN45 cell proliferation (evaluated using EdU incorporation assay), significantly blocked the cell cycle in G1 phase (assessed using flow cytometry) and significantly decreased mRNA and protein expression levels of cyclin D1 (assessed by reverse transcription­quantitative PCR and western blotting, respectively). Furthermore, the number of apoptotic bodies and apoptosis rate were markedly elevated and mitochondrial membrane potential was markedly decreased. Moreover, mRNA and protein expression levels of Bax increased and Bcl­2 decreased markedly in MKN45 cells following transfection with the CTPS­overexpression vector. The proliferation rate increased, percentage of G1/G0­phase cells decreased and apoptosis was attenuated in cells transfected with the R294D­CTPS mutant vector and this mutation did not lead to formation of cytoophidia. The results of the present study suggested that formation of CTPS cytoophidia inhibited proliferation and promoted apoptosis in MKN45 cells. These results may provide insights into the role of CTPS cytoophidia in cancer cell proliferation and apoptosis.

[Effects of Betulinic acid on apoptosis in human gastric cancer SGC-7901 cells].

Objective: To investigate the effects of betulinic acid on apoptosis of human gastric cancer SGC-7901 cells. Methods: The human gastric cancer SGC-7901cells were divided in to 4 groups, and each group was set with 3 replicates. The SGC-7901cells in control group were not treated with betulinic acid; the other 3 experimental groups were treated with betulinic acid at the concentrations of 10, 20 and 30 mg/L, respectively; each group was incubated in a 5% carbon dioxide incubator for 48 h. Laser confocal microscope was used to observe morphological changes of SGC-7901 cells; Flow cytometry was applied to determine apoptosis rate and mitochondrial membrane potential. The mRNA and protein levels of Bcl-2, Bax and Caspase-3 were also detected by qRT-PCR and western blot respectively. Results: Compared with the control group, SGC-7901 cells in the treated group at final concentrations of 10, 20 and 30 mg/L shrinked, appeared apoptosis body along with nuclear splitting. The percentage of cells in early and advanced period of apoptosis were markedly increased (P＜0.05 or P＜0.01), mitochondrial membrane potential was obviously reduced (P＜0.05 or P＜0.01). qRT-PCR and western blot analysis showed that the mRNA and protein expressions of Bax and Caspase-3 were increased significantly (P＜0.01), while the expressions of Bcl-2 were decreased significantly (P＜0.01). Conclusion: Within a certain range of concentrations, betulinic acid induces cell apoptosis by regulating the expression of Bcl-2, Bax and Caspase-3 in human gastric cancer.

The α-Subunit of the Chloroplast ATP Synthase of Tomato Reinforces Resistance to Gray Mold and Broad-Spectrum Resistance in Transgenic Tobacco.

Chloroplast ATP synthase (cpATPase) is responsible for ATP production during photosynthesis. Our previous studies showed that the cpATPase CF1 α subunit (AtpA) is a key protein involved in Clonostachys rosea-induced resistance to the fungus Botrytis cinerea in tomato. Here, we show that expression of the tomato atpA gene was upregulated by B. cinerea and Clonostachys rosea. The tomato atpA gene was then isolated, and transgenic tobacco lines were obtained. Compared with untransformed plants, atpA-overexpressing tobacco showed increased resistance to B. cinerea, characterized by reduced disease incidence, defense-associated hypersensitive response-like reactions, balanced reactive oxygen species, alleviated damage to the chloroplast ultrastructure of leaf cells, elevated levels of ATP content and cpATPase activity, and enhanced expression of genes related to carbon metabolism, photosynthesis, and defense. Incremental Ca2+ efflux and steady H+ efflux were observed in transgenic tobacco after inoculation with B. cinerea. In addition, overexpression of atpA conferred enhanced tolerance to salinity and resistance to the fungus Cladosporium fulvum. Thus, AtpA is a key regulator that links signaling to cellular redox homeostasis, ATP biosynthesis, and gene expression of resistance traits to modulate immunity to pathogen infection and provides broad-spectrum resistance in plants in the process.

Meta-analysis of the clinicopathological significance of miRNA-145 in breast cancer.

Low expression of tumor suppressor microRNA (miRNA) and high expression of carcinogenic miRNA promote the occurrence and progression of human cancer. Most studies show that miR-145 is a tumor suppressor miRNA, and is closely related to the clinicopathology of breast cancer. However, the results are still inconsistent. Therefore, we conducted a meta-analysis on the basis of eligible studies to summarize the possible correlation between miR-145 and the clinicopathology and prognosis of breast cancer. Using PubMed, Embase, Web of Science, Wanfang and CNKI, we searched all published papers written in either English or Chinese on miR-145 expression in breast cancer from 1990 to November 2019 for meta-analysis. We used standardized mean difference (SMD) to evaluate the differential expression of miR-145 in breast cancer tissues and adjacent normal tissues or normal breast tissues. We found that miR-145 expression was significantly lower in breast cancer tissues than that in adjacent normal tissues (SMD = -2.93, P<0.0001) and in healthy women (SMD = -0.52, P=0.009). miR-145 expression was lower in breast cancer patients with ER-positive (SMD = 0.65, P<0.001), HER-2-positive (SMD = -1.04, P<0.001), compared with their counterparts, respectively. In addition, breast cancer patients with low expression of miR-145 had larger tumor diameters (SMD = -1.97, P<0.001) and lymph node metastasis (SMD = -1.75, P<0.001) that are unfavorable prognostic factors. Conclusion: Low miR-145 is observed in breast cancer, which is closely related to molecular subtypes and unfavorable factors of breast cancer. These findings indicate that miR-145 is tumor suppressor miRNA, and may be a potential diagnostic and prognostic marker in breast cancer.

Toosendanin induces apoptosis of MKN­45 human gastric cancer cells partly through miR­23a­3p­mediated downregulation of BCL2.

Toosendanin (TSN) is a tetracyclic triterpenoid extracted from Melia toosendan Sieb, et Zucc, which primarily grows in specific areas of China. Although toosendanin (TSN) exerts antitumoral effects on various human cancer cells, its influence on gastric cancer (GC) is remains to be elucidated. MicroRNAs (miRNAs/miRs) serve crucial roles in apoptosis and proliferation of cancer cells. miR­23a­3p has been shown to be associated with human GC; however, the specific function of miR­23a­3p in GC remains unclear. Therefore, the present study aimed to elucidate the role of miR­23a­3p in the regulation of GC cell proliferation and apoptosis induced in vitro by TSN treatment. Subsequently, apoptosis­related genes expression levels were quantified by reverse transcription­quantitative PCR and western blot analysis, respectively, and the target relationship between miR­23a­3p and BCL2 was determined by luciferase reporter gene analysis. Additionally, cell proliferation and apoptosis experiments were carried out. The results indicated that TSN inhibited proliferation and induced apoptosis in MKN­45 cells. Moreover, it upregulated the expression of miR­23a­3p. B­cell lymphoma­2 (BCL2) was identified as a potential target gene of miR­23a­3p, which was demonstrated to bind to the 3'­untranslated region of BCL2 mRNA, as detected by the luciferase reporter assay. Further studies revealed that BCL2 expression was downregulated following overexpression of miR­23a­3p. In addition, the overexpression of the miR­23a­3p inhibited proliferation, induced G1 arrest and increased apoptosis in MKN­45 cells. The results of the present study demonstrated that miR­23a­3p inhibited proliferation and induced apoptosis of GC cells, which may be attributable to its direct targeting of BCL2. These results may provide a novel insight into the apoptosis of GC cells, and may lead to investigations into the mechanisms of the effects of TSN.

[Effect of betulinic acid on proliferation of human gastric cancer SGC-7901 cells].

Objective: Human gastric cancer SGC-7901 cells were treated with betulinic acid(BA)at the concentrations of 0, 10, 20, and 30 µg/ml, and treated with conventional chemotherapeutic drug 5-Fu as a positive control to explore its effect on cell proliferation. Trypan blue and GIEMSA staining method were used to investigate the effect of BA on cell growth inhibition and clone formation. EdU method and flow cytometry were used to explore the proliferation and cell cycle of SGC-7901 cells after treated with BA, respectively. qRT-PCR and Western blot were also applied to determine the mRNA and protein levels of cyclin D1 and cyclin B1. Results: The cell growth inhibition rate was increased after treated with different concentrations of BA in SGC-7901 cells(P＜0.05). After treated for 48 h, BA decreased the clone information and cell proliferation of SGC-7901 cells markedly in dose-and time-dependent manners (P＜0.01). Flow cytometry analysis showed that BA obviously increased the proportion of SGC-7901 cells in G1 phase but decreased the proportion of those in S phase. qRT-PCR and Western blot analysis showed that the mRNA and protein levels of cyclin D1 and cyclin B1 were significantly downregulated by BA at different concentrations(P＜0.01). Compared with the 5-Fu control group, when the concentration of BA was 20 µg/ml and 30 µg/ml, the cell proliferation ability was significantly decreased, the cell cycle was inhibited, and the expression of cyclin was reduced (all P＜0.05). Conclusion: The betulinic acid regulates the proliferation of SGC-7901 cells by inhibiting the expressions of cyclin D1 and cyclin B1, which leads to cell cycle arrest and proliferative inhibition.

Direct binding of RNF8 to SUMO2/3 promotes cell survival following DNA damage.

Ring finger protein 8 (RNF8), an FHA/RING domain containing E3 ubiquitin ligase, is critical in supporting genome integrity by facilitating the assembly of multiple DNA repair proteins at DNA lesions following DNA damage. In the present study, a search for novel binding partners of RNF8 was performed using a yeast two­hybrid screening assay, and small ubiquitin­like modifier (SUMO)2/3 was identified as one of the major RNF8­binding candidates. GST pull­down and immunoprecipitation assays revealed that RNF8 bound directly and noncovalently to SUMO2/3, but not to SUMO1, and that the FHA domain of RNF8 was required for the binding to SUMO2/3. Furthermore, RNF8 co­localized with SUMO2/3 at sites of DNA lesions in response to ionizing radiation, as revealed by immunofluorescence assay. Survival assay indicated that the depletion of RNF8 and SUMO2/3 resulted in decreased cellular resistance to genotoxic stress. These data suggested that the binding of RNF8 to SUMO2/3 promoted the response to DNA damage.

Catalyst System for Hydrogenation Catalysis Based on Multiarm Hyperbranched Polymer Templated Metal (Au, Pt, Pd, Cu) Nanoparticles.

With a hyperbranched poly(amidoamine) core and many water-soluble poly(ethylene glycol) monomethyl ether arms connected by pH-sensitive acylhydrazone bonds, multiarm hyperbranched polymer was used as nanoreactor and reductant to prepare metal nanoparticles endowed with intelligence and biocompatibility. The multiarm hyperbranched polymer encapsulated nanoparticles (NPs) showed excellent catalytic activity for hydrogenation, thus an excellent catalyst system for hydrogenation was established. The rate constants could reach as high as 3.48 L·s-1·m-2, which can be attributed to the lack of surface passivation afforded by the multiarm hyperbranched polymer.

An integrated strategy for the rapid extraction and screening of phosphatidylcholines and lysophosphatidylcholines using semi-automatic solid phase extraction and data processing technology.

This study attempts to establish a comprehensive strategy for the rapid extraction and screening of phosphatidylcholines (PCs) and lysophosphatidylcholines (LysoPCs) in biological samples using semi-automatic solid phase extraction (SPE) and data processing technology based on ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS). First, the Ostro sample preparation method (i.e., semi-automatic SPE) was compared with the Bligh-Dyer method in terms of substance coverage, reproducibility and sample preparation time. Meanwhile, the screening method for PCs and LysoPCs was built through mass range screening, mass defect filtering and diagnostic fragments filtering. Then, the Ostro sample preparation method and the aforementioned screening method were combined under optimal conditions to establish a rapid extraction and screening platform. Finally, this developed method was validated and applied to the preparation and data analysis of tissue samples. Through a systematic evaluation, this developed method was shown to provide reliable and high-throughput experimental results and was suitable for the preparation and analysis of tissue samples. Our method provides a novel strategy for the rapid extraction and analysis of functional phospholipids. In addition, this study will promote further study of phospholipids in disease research.

C-terminus of MUC16 activates Wnt signaling pathway through its interaction with ß-catenin to promote tumorigenesis and metastasis.

MUC16/CA125 has been identified as a prominent cancer biomarker, especially for epithelial ovarian cancers, in clinical test for over three decades. Due to its huge mass, limited knowledge of MUC16 was acquired previously. By utilizing a well characterized self-made MUC16 monoclonal antibody, we identified the endogenous interaction between a C-terminal fragment of MUC16 (MUC16C) and ß-catenin for the first time, and further elucidated that trans-activation domain of ß-catenin is required for this interaction. Such interaction could activate the Wnt/ß-catenin signaling pathway by facilitating cytosol-nucleus transportation of ß-catenin, consequently induce cell proliferation and the migration, eventually lead to tumorigenesis and metastasis in nude mice. Consistently, knockdown of MUC16 significantly weakened the capabilities of cells for proliferation and migration. Based on our discovery, we suggest that MUC16 appears as an attractive target for the development of effective anticancer drugs.

Validation of biomarkers in cardiotoxicity induced by Periplocin on neonatal rat cardiomyocytes using UPLC-Q-TOF/MS combined with a support vector machine.

Corex Periplocae (the root of Periploca sepium Bge) has been widely used in clinics. Periplocin, as one of the components of cardiac glycosides in Corex Periplocae, easily triggers cardiotoxicity when used improperly. To evaluate the toxicity of Periplocin, we used UPLC-Q-TOF/MS to investigate metabolic profiles on neonatal rat cardiomyocytes exposed to high and low doses of Periplocin (0.2 mmol/L, 0.4 mmol/L). Finally, we identified 11 biomarkers associated with toxicity through multivariate statistical analysis. A "supervised" Support Vector Machine (SVM) study was used to optimize and verify the reliability of these biomarkers. In these biomarkers, all biomarkers, including carnitine, acetylcarnitine, lysoPC(16:0), proline, glutamic acid, pyroglutamic acid, leucine, pantothenic acid, tryptophan, indoleacrylic acid and citric acid, revealed a downward trend with the increase of dosage. Moreover, pathway analysis showed that these metabolites were associated with amino acid metabolism, energy metabolism and sphingolipid metabolism, which contributes to a further understanding of the toxicity mechanism of Corex Periplocae and its clinical safety. Additionally, we demonstrate that an UPLC-Q-TOF/MS-based metabolomic approach is a powerful tool and provides a promising approach for assessing the toxicity of traditional Chinese medicine and drug safety screening.

Correction: A Co(2+)-selective and chirality-sensitive supermolecular metallohydrogel with a nanofiber network skeleton.

Correction for 'A Co(2+)-selective and chirality-sensitive supermolecular metallohydrogel with a nanofiber network skeleton' by Xiaojuan Wang et al., Nanoscale, 2016, DOI: 10.1039/c6nr00822d.

A Co²âº-selective and chirality-sensitive supermolecular metallohydrogel with a nanofiber network skeleton.

This paper introduces a new metallohydrogel precursor that offers a peculiar gelation response to Co(2+) at pH 7-8. It is notable that the stability of this metallohydrogel is significantly dependent on its enantiomeric purity. In addition to the expected multi-stimuli responsive properties, including thixotropy, as well as re-assembly properties on adding HCl, this metallohydrogel possesses excellent self-healing behavior, which is uncommon in low-molecular-weight gelators. Electron microscopy (EM) studies revealed that the cryodried remains of this gel presented as well an organized three dimensional (3D) network of fibrils. This interesting metallohydrogel shows potential for developing new soft materials with drug delivery and catalysis properties.

A Systematic Strategy for Screening and Application of Specific Biomarkers in Hepatotoxicity Using Metabolomics Combined With ROC Curves and SVMs.

Current studies that evaluate toxicity based on metabolomics have primarily focused on the screening of biomarkers while largely neglecting further verification and biomarker applications. For this reason, we used drug-induced hepatotoxicity as an example to establish a systematic strategy for screening specific biomarkers and applied these biomarkers to evaluate whether the drugs have potential hepatotoxicity toxicity. Carbon tetrachloride (5 ml/kg), acetaminophen (1500 mg/kg), and atorvastatin (5 mg/kg) are established as rat hepatotoxicity models. Fifteen common biomarkers were screened by multivariate statistical analysis and integration analysis-based metabolomics data. The receiver operating characteristic curve was used to evaluate the sensitivity and specificity of the biomarkers. We obtained 10 specific biomarker candidates with an area under the curve greater than 0.7. Then, a support vector machine model was established by extracting specific biomarker candidate data from the hepatotoxic drugs and nonhepatotoxic drugs; the accuracy of the model was 94.90% (92.86% sensitivity and 92.59% specificity) and the results demonstrated that those ten biomarkers are specific. 6 drugs were used to predict the hepatotoxicity by the support vector machines model; the prediction results were consistent with the biochemical and histopathological results, demonstrating that the model was reliable. Thus, this support vector machine model can be applied to discriminate the between the hepatic or nonhepatic toxicity of drugs. This approach not only presents a new strategy for screening-specific biomarkers with greater diagnostic significance but also provides a new evaluation pattern for hepatotoxicity, and it will be a highly useful tool in toxicity estimation and disease diagnoses.

Screening and validation for plasma biomarkers of nephrotoxicity based on metabolomics in male rats.

Currently, drug-induced nephrotoxicity is widespread and seriously affects human health. However, the conventional indexes of renal function lack sensitivity, leading to a delay in the detection of nephrotoxicity. Therefore, we need to identify more sensitive indexes for evaluating nephrotoxicity. In this study, we used gentamicin (100 mg kg-1), etimicin (100 mg kg-1) and amphotericin B (4 mg kg-1) to establish renal injury models in rats, and we collected information using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry in the screening stage. Thirteen nephrotoxicity metabolites were selected after multivariate statistical and integration analyses. Then, we conducted trend analysis to select 5 nephrotoxicity biomarkers [thymidine, LysoPC(16:1), LysoPC(18:4), LysoPC(20:5), and LysoPC(22:5)] whose content changed consistently at different timepoints after drug administration. To verify the sensitivity and specificity of these biomarkers for nephrotoxicity, receiver operating characteristic (ROC) and support vector machine (SVM) analyses were applied. The area under the curve of the 5 biomarkers were 0.806-0.901 at the 95% confidence interval according to the ROC analysis. We used the SVM classified model to verify these biomarkers, and the prediction rate was 95.83%. Therefore, the 5 biomarkers have strong sensitivity and high accuracy; these biomarkers are more sensitive indexes for evaluating renal function to identify nephrotoxicity and initiate prompt treatment.

The in situ synthesis of Ag/amino acid biopolymer hydrogels as mouldable wound dressings.

This manuscript introduces a one-pot fabrication procedure for the preparation of supramolecular hybrid hydrogels from low-cost commercially available natural products through a "green" strategy. In particular, the hybrid hydrogels, which are developed with Fmoc-Glu-OMe, silver nanoparticles and chitosan, exhibit outstanding antibacterial properties and can be regarded as excellent mouldable wound healing biomaterials.

Effects of low temperature on mRNA and small RNA transcriptomes in Solanum lycopersicoides leaf revealed by RNA-Seq.

The plant low temperature tolerance mechanisms have been studied in the Arabidopsis, tomato, Solanum commersonii, Solanum tuberosum, Chorispora bungeana, and Chinese cabbage at the transcriptional level. Some genome-wide works to identify cold-regulated genes, but no comprehensive research of the Solanum lycopersicoides transcriptome under low temperature stress have been performed. S. lycopersicoides is more freeze-tolerant than the cultivated tomato. We analyzed the low temperature transcriptomes and small RNA fractions of S. lycopersicoides leaf tissue using an Illumina platform for high-throughput RNA sequencing (RNA-seq). There were 59,286 unigenes obtained using de novo assembly, and 2052 down-regulated and 2409 up-regulated unigenes were identified in response to chilling. The expression of six cold-regulated genes was confirmed by qPCR. Some biological processes were showed, by gene ontology term enrichment analysis of the cold-regulated genes, including 'response to stimulus', 'signaling', and 'cell killing' in the response of S. lycopersicoides to chilling. In addition, we identified a total of 952 novel miRNA candidates that may regulate relevant target genes. Our data indicated that certain miRNAs (e.g., sly-miR156a, sly-miR397, and unconservative_SL2.50ch00_21686) play roles in response to low temperature stress. Sequencing of mRNAs and miRNAs revealed new genes and allowed us to have new assumptions for a low temperature tolerance mechanism.

A novel approach to the simultaneous extraction and non-targeted analysis of the small molecules metabolome and lipidome using 96-well solid phase extraction plates with column-switching technology.

This study combines solid phase extraction (SPE) using 96-well plates with column-switching technology to construct a rapid and high-throughput method for the simultaneous extraction and non-targeted analysis of small molecules metabolome and lipidome based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. This study first investigated the columns and analytical conditions for small molecules metabolome and lipidome, separated by an HSS T3 and BEH C18 columns, respectively. Next, the loading capacity and actuation duration of SPE were further optimized. Subsequently, SPE and column switching were used together to rapidly and comprehensively analyze the biological samples. The experimental results showed that the new analytical procedure had good precision and maintained sample stability (RSD<15%). The method was then satisfactorily applied to more widely analyze the small molecules metabolome and lipidome to test the throughput. The resulting method represents a new analytical approach for biological samples, and a highly useful tool for researches in metabolomics and lipidomics.

Screening, verification, and optimization of biomarkers for early prediction of cardiotoxicity based on metabolomics.

Drug-induced cardiotoxicity seriously affects human health and drug development. However, many conventional detection indicators of cardiotoxicity exhibit significant changes only after the occurrence of severe heart injuries. Therefore, we investigated more sensitive and reliable indicators for the evaluation and prediction of cardiotoxicity. We created rat cardiotoxicity models in which the toxicity was caused by doxorubicin (20 mg/kg), isoproterenol (5 mg/kg), and 5-fluorouracil (125 mg/kg). We collected data from rat plasma samples based on metabolomics using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Following multivariate statistical and integration analyses, we selected 39 biomarker ions of cardiotoxicity that predict cardiotoxicity earlier than biochemical analysis and histopathological assessment. Because drugs with different toxicities may cause similar metabolic changes compared with other noncardiotoxic models (hepatotoxic and nephrotoxic models), we obtained 10 highly specific biomarkers of cardiotoxicity. We subsequently used a support vector machine (SVM) to develop a predictive model to verify and optimize the exclusive biomarkers. l-Carnitine, 19-hydroxydeoxycorticosterone, LPC (14:0), and LPC (20:2) exhibited the strongest specificities. The prediction rate of the SVM model is as high as 90.0%. This research provides a better understanding of drug-induced cardiotoxicity in drug safety evaluations and secondary development and demonstrates novel ideas for verification and optimization of biomarkers via metabolomics.