Research Advances in Amorphous-Crystalline Heterostructures Toward Efficient Electrochemical Applications.

Interface engineering of heterostructures has proven a promising strategy to effectively modulate their physicochemical properties and further improve the electrochemical performance for various applications. In this context related research of the newly proposed amorphous-crystalline heterostructures have lately surged since they combine the superior advantages of amorphous- and crystalline-phase structures, showing unusual atomic arrangements in heterointerfaces. Nonetheless, there has been much less efforts in systematic analysis and summary of the amorphous-crystalline heterostructures to examine their complicated interfacial interactions and elusory active sites. The critical structure-activity correlation and electrocatalytic mechanism remain rather elusive. In this review, the recent advances of amorphous-crystalline heterostructures in electrochemical energy conversion and storage fields are amply discussed and presented, along with remarks on the challenges and perspectives. Initially, the fundamental characteristics of amorphous-crystalline heterostructures are introduced to provide scientific viewpoints for structural understanding. Subsequently, the superiorities and current achievements of amorphous-crystalline heterostructures as highly efficient electrocatalysts/electrodes for hydrogen evolution reaction, oxygen evolution reaction, supercapacitor, lithium-ion battery, and lithium-sulfur battery applications are elaborated. At the end of this review, future outlooks and opportunities on amorphous-crystalline heterostructures are also put forward to promote their further development and application in the field of clean energy.

Metal-Organic Frameworks for Electrocatalytic Sensing of Hydrogen Peroxide.

The electrochemical detection of hydrogen peroxide (H2O2) has become more and more important in industrial production, daily life, biological process, green energy chemistry, and other fields (especially for the detection of low concentration of H2O2). Metal organic frameworks (MOFs) are promising candidates to replace the established H2O2 sensors based on precious metals or enzymes. This review summarizes recent advances in MOF-based H2O2 electrochemical sensors, including conductive MOFs, MOFs with chemical modifications, MOFs-composites, and MOF derivatives. Finally, the challenges and prospects for the optimization and design of H2O2 electrochemical sensors with ultra-low detection limit and long-life are presented.

Activity Trends of Binary Silver Alloy Nanocatalysts for Oxygen Reduction Reaction in Alkaline Media.

The electrocatalytic activity of Pt-based alloys exhibits a strong dependence on their electronic structures, but a relationship between electronic structure and oxygen reduction reaction (ORR) activity in Ag-based alloys is still not clear. Here, a vapor deposition based approach is reported for the preparation of Ag75 M25 (M = Cu, Co, Fe, and In) and Agx Cu100-x (x = 0, 25, 45, 50, 55, 75, 90, and 100) nanocatalysts and their electronic structures are determined by valence band spectra. The relationship of the d-band center and ORR activity exhibits volcano-shape behaviors, where the maximum catalytic activity is obtained for Ag75 Cu25 alloys. The ORR enhancement of Ag75 Cu25 alloys originates from the 0.12 eV upshift in d-band center relative to pure Ag, which is different from the downshift in the d-band center in Pt-based alloys. The activity trend for these Ag75 M25 alloys is in the order of Ag75 Cu25 > Ag75 Fe25 > Ag75 Co25 . These results provide an insight to understand the activity and stability enhancement of Ag75 Cu25 and Ag50 Cu50 catalysts by alloying.

Toxicogenomic analysis of the particle dose- and size-response relationship of silica particles-induced toxicity in mice.

This study investigated the relationship between particle size and toxicity of silica particles (SP) with diameters of 30, 70, and 300 nm, which is essential to the safe design and application of SP. Data obtained from histopathological examinations suggested that SP of these sizes can all induce acute inflammation in the liver. In vivo imaging showed that intravenously administrated SP are mainly present in the liver, spleen and intestinal tract. Interestingly, in gene expression analysis, the cellular response pathways activated in the liver are predominantly conserved independently of particle dose when the same size SP are administered or are conserved independently of particle size, surface area and particle number when nano- or submicro-sized SP are administered at their toxic doses. Meanwhile, integrated analysis of transcriptomics, previous metabonomics and conventional toxicological results support the view that SP can result in inflammatory and oxidative stress, generate mitochondrial dysfunction, and eventually cause hepatocyte necrosis by neutrophil-mediated liver injury.

Direct regeneration of waste LiFePO4 cathode materials with a solid-phase method promoted by activated CNTs.

Annually increasing electric vehicles will undoubtedly end in tremendous amount of waste LiFePO4 (LFP) batteries. In this work, a highly-efficient and easy-going solid-phase method is proposed for direct regeneration of the waste LFP cathode material (W-LFP). The W-LFP is successfully regenerated via heat treatment with the addition of Li2CO3, CNTs and glucose. After activation, the dispersibility of CNTs in water is improved, making it easier to mix well with other materials. Also, the hydroxyl and carboxyl groups on CNTs have a certain degree of reducibility, which is conducive to the reduction of Fe3+ to Fe2+. After subsequent heat treatment, the three-dimensional conductive network composed of CNTs greatly enhances the conductivity and the ionic diffusion coefficient of LFP, thereby improving its electrochemical performance. Meanwhile, the decay and regeneration mechanisms of LFP are investigated by characterization and electrochemical testing. The regenerated LFP achieves an excellent specific capacity of 155.47 mAh/g at 0.05 C, which is around 99% that of new LFP. Additionally, the costs of main consumption in the regeneration process only account for 33.7% the price of new LFP. This low-cost, high-value-added and solid-phase direct regeneration process is proved to have great economic and energy-saving potential, which is promising for recycling the waste LFP cathode materials.

Structural and electrochemical progress of O3-type layered oxide cathodes for Na-ion batteries.

Sodium-ion batteries (SIBs) have attracted great attention being the most promising sustainable energy technology owing to their competitive energy density, great safety and considerable low-cost merits. Nevertheless, the commercialization process of SIBs is still sluggish because of the difficulty in developing high-performance battery materials, especially the cathode materials. The discovery of layered transition metal oxides as the cathode materials of SIBs brings infinite possibilities for practical battery production. Thereinto, the O3-type layered transition metal oxides exhibit attractive advantages in terms of energy density benefiting from their higher sodium content compared to other kinds of layered transition metal oxides. Enormous research studies have largely put forward their progress and explored a wide range of performance improvement approaches from the morphology, coating, doping, phase structure and redox aspects. However, the progress is scattered and has not logically evolved, which is not beneficial for the further development of more advanced cathode materials. Therefore, our work aims to comprehensively review, classify and highlight the most recent advances in O3-type layered transition metal oxides for SIBs, so as to scientifically cognize their progress and remaining challenges and provide reasonable improvement ideas and routes for next-generation high-performance cathode materials.

Corrigendum: Diplatin, a Novel and Low-Toxicity Anti-Lung Cancer Platinum Complex, Activation of Cell Death in Tumors via a ROS/JNK/p53-Dependent Pathway, and a Low Rate of Acquired Treatment Resistance.

[This corrects the article DOI: 10.3389/fphar.2019.00982.].

Rh particles in N-doped porous carbon materials derived from ZIF-8 as an efficient bifunctional electrocatalyst for the ORR and HER.

Durable and efficient electrocatalysts toward the oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER) are crucial to the development of sustainable energy conversion. In this article, we report a highly active bifunctional electrocatalyst derived from ZIF-8 through simple heat-treatment activation. The resultant catalyst is enriched with Rh nanoparticles in the carbon matrix, showing excellent ORR performance with a half-wave potential (E 1/2) of 0.803 V in alkaline electrolytes; it is simultaneously active for catalyzing the HER with an overpotential of 89 mV to reach a current density of 10 mA cm2 in acidic electrolytes. The prepared RhNC-900 catalyst (1.47 wt% Rh) is comparable to the commercial Pt/C catalyst (20 wt% Pt) in terms of the ORR in alkaline media and might inspire new ideas for the development of fuel cells and water splitting.

Engineering Two-Dimensional PdAgRh Nanoalloys by Surface Reconstruction for Highly Active and Stable Formate Oxidation Electrocatalysis.

Promoting the formate oxidation reaction (FOR) is central to develop promising direct formate fuel cells, but current electrocatalysts are suffering from low activity and ultrapoor stability. Herein, the ternary PdAgRh nanoalloys with ultrathin two-dimensional architecture are for the first time synthesized and employed as a novel class of electrocatalysts for the FOR. Benefitting from unique nanostructure as well as oxophilic Rh surface oxides, the Pd55Ag30Rh15/C electrocatalyst demonstrates an exceptional FOR activity of 1.85 A mgPd-1, showing a 4.74-fold improvement compared to the commercial Pd/C, and retains the current density of 150 mA mgPd-1 after a long-term test, representing the greatest durability among all available FOR electrocatalysts. More strikingly, extending the upper limit potential (ULP) of cyclic voltammetry is revealed to facilitate the surface reconstruction of the Pd55Ag30Rh15/C electrocatalyst to in situ form Ag surface oxides (Ag-O), resulting in a highly active and stable Pd/Ag-O interface at the atomic scale, which considerably boost the FOR performance. In particular, the reconstructed Pd55Ag30Rh15/C electrocatalyst exhibits a mass activity of 3.26 A mgPd-1 with 74.2% of initial activity retained after 1000 cycles. This work showcases an effective strategy to tune surface reconstruction on multimetallic nanoalloys for robust FOR electrocatalysts and beyond.

Surface reconstruction of AgPd nanoalloy particles during the electrocatalytic formate oxidation reaction.

Formate is a kind of carbon-neutral fuel that can be synthesized by electrochemical conversion of CO2, however, the generated aqueous formate electrolyte is still short of potential application. Here, formate solution is proposed to be utilized as anode fuels of direct formate fuel cells through the formate oxidation reaction (FOR), and graphene supported AgPd nanoalloys (AgPd/rGO) are prepared to catalyze the FOR. Specifically, the mass activity of the as-prepared Ag49Pd51/rGO catalyst is 4.21 A mg-1Pd and the retention activity of Ag49Pd51/rGO is 49.1% of initial activity after successive 500 cycles, which is 2.48 and 3.03 times higher than that of unsupported Ag51Pd49 nanoalloys. When increasing the positive scan limit from 0.0 to 0.8 V, the mass activity of the Ag49Pd51/rGO catalyst increases from 2.32 to 6.03 A mg-1Pd and Pd surface coverage increases from 51.87% to 62.42%, indicating the occurrence of surface reconstruction where Pd atoms migrate to the surface of AgPd nanoalloys, and less intensive reconstruction is observed in unsupported Ag51Pd49 nanoalloys, whose mass activity increases from 1.35 to 2.49 A mg-1Pd. The driving force and kinetic path are calculated for the surface reconstruction induced by the adsorption of H, O and C atoms, in the case of C atoms on graphene, the segregation energy of surface Pd atoms in the AgPd nanoalloy is -1.16 eV, and the activation energy for the migration of subsurface Pd atoms to the surface is 0.54 eV, which are lower than the segregation (0.03 eV) and activation (2.06 eV) energy on a clean alloy surface.

Anti-allergic activities of 5,7-dimethoxy-3,4'-dihydroxyflavone via inhalation in rat allergic models.

Various studies have shown that flavones have several pharmacological activities including anti-allergy activities. However, the bioavailability of oral flavones is very low, and whether inhaled administration can improve efficacy in respiratory disease models is unclear. In the present study, the anti-allergic activities of inhaling 5,7-dimethoxy-3,4'-dihydroxyflavone (MHF), a synthetic flavonoid, was investigated by comparison with disodium cromoglycate (DSCG) and nedocromil sodium (NS) in rat allergic models. In an anti-DNP-IgE-induced asthmatic model, inhaled MHF dose-dependently inhibited the increase in airway resistance after antigen challenge. In an ovalbumin (OVA)-induced asthmatic model, inhaled MHF showed significant suppression of airway hyperresponsiveness; a decrease in eosinophil and neutrophil counts, IL-4, IL-5 and leukotriene D4 in bronchoalveolar lavage fluid; a reduction in total IgE and OVA-specific IgE levels in serum; and suppression of eosinophil infiltration in lung tissue after antigen challenge. The efficacy of inhaled MHF was comparable to that of NS and DSCG. In conclusion, based on these findings, the report for the first time that that inhaled MHF may be a potential drug for the treatment of allergic asthma.

In situ high-potential-driven surface restructuring of ternary AgPd-Ptdilute aerogels with record-high performance improvement for formate oxidation electrocatalysis.

Engineering nanoparticle surfaces driven by various gas atmospheres has attracted intensive attention in the design of efficient electrocatalysts for sustainable energy applications. However, the development of a more facile and efficient in situ engineering strategy under electrochemical testing conditions to achieve surface-reconstruction-induced high performance is significantly lacking. Herein, for the first time, we report in situ high-potential-driven restructuring in ternary AgPdPt aerogels with dilute Pt (AgPd-Ptdilute) during the electrochemical cyclic voltammetry testing for the alkaline formate oxidation reaction (FOR), in which the upper potential limit is ingeniously extended to the Ag redox region. Impressively, the resulting AgPd-Ptdilute aerogel displayed remarkable structural and compositional reconstruction in an alkaline environment. Our comprehensive results revealed that the high-potential cycling induces unique Ag outward diffusion to form an enriched PdPt metallic surface atomically coupled with amorphous Ag2O, which provides more opportunities to expose abundant active sites and induce robust electronic structure modulation. Notably, the surface-restructured AgPd-Ptdilute aerogel achieved record-high activity for FOR when the upper potential limit was extended to 1.3 V, exhibiting an unprecedented 5-fold improvement in activity compared to that of the commercial Pd/C. Moreover, it also offered greatly enhanced electrochemical stability with negligible activity decay after 500 cycles. This work gives a good understanding of surface reconstruction during such a novel high-potential-driven cycling process and opens a new door to designing more efficient electrocatalysts for FOR and beyond.

Diplatin, a Novel and Low-Toxicity Anti-Lung Cancer Platinum Complex, Activation of Cell Death in Tumors via a ROS/JNK/p53-Dependent Pathway, and a Low Rate of Acquired Treatment Resistance.

Background: Platinum-based drugs prevail as the main treatment of lung cancer; this is caused by their relative effectiveness despite known side effects, such as neurotoxicity. The risk reward of the treatment and side effects is confronted when dosage is considered and when resistance to treatment develops. Development of new compounds that improve effectiveness and safety profiles addresses this ongoing need in clinical practice. Objectives: The novel water-soluble platinum complex, diplatin, was synthesized, and its antitumor potency and toxicology profile were evaluated in murine xenograft tumor models and in lung cancer cell lines. Methods: The effects of diplatin, cisplatin (DDP), and carboplatin (CBP) on the viability of nine lung tumor cell lines and one normal human lung epithelial cell line were evaluated using the MTT assay. Therapeutic index was calculated as LD50/ED50 to identify and compare the ideal therapeutic windows of the above compounds. Diplatin's antitumor effects were assessed in lung xenograft tumors of nude mice; molecular mechanisms of therapeutic effects were identified. Results: Diplatin had desirable IC50 compared to CBP in a variety of cultured tumor cells, notably lung tumor cells. In the mouse xenograft lung tumor, diplatin led to a substantially improved therapeutic index when compared to the effects of DDP and CBP. Importantly, diplatin inhibited the growth of DDP-resistant lung tumor cells. Diplatin's mode of action was characterized to be through cell cycle arrest in the G2/M phase and induction of lung tumor apoptosis via ROS/JNK/p53-mediated pathways. Conclusion: Diplatin was observed to have antitumor effects in mice with both greater potency and safety compared with DDP and CBP. These observations indicate that diplatin is promising as a potential treatment in future clinical applications.

Dilute Au-Containing Ag Nanosponges as a Highly Active and Durable Electrocatalyst for Oxygen Reduction and Alcohol Oxidation Reactions.

Zero-dimensional nanoparticles (NPs) have been demonstrated as the promising class of catalysts for various chemical and electrochemical reactions. However, the emerging Au-Ag NP catalysts suffer from single functionality, limited activity enhancement, and unsatisfactory stability problems. Here, we report a facile kinetically controlled solution method to prepare a new class of Au-Ag nanoporous sponges (NSs) composed of three-dimensional networks without using additional stabilizing agents at room temperature. The unexpected shift of the d-band center in our Au-Ag NSs was observed for the first time in Au-Ag bimetallic systems, which effectively activates the Au-Ag NSs for electrochemical reactions. The robust electronic effect coupled with abundant accessible active sites from the hierarchically porous architecture make the bare Au-Ag NSs a superior multifunctional catalyst for oxygen reduction, ethylene glycol (EG) oxidation, and glucose oxidation reactions compared to the commercial Pt/C electrocatalyst in alkaline medium. The optimized AuAg3.2 NSs deliver a mass activity of 1.26 A mgAu-1 toward oxygen reduction reaction, which is ∼8.2 times as high as that of the Pt/C electrocatalyst, simultaneously showing outstanding stability with negligible activity decay after 10 000 cycles. For the anodic reactions, these AuAg3.2 NSs show extremely high activity and stability toward both EG and glucose catalytic oxidation reactions with a higher mass activity of 7.58 and 1.48 A mgAu-1, about 3- and 18.5-fold enhancement than Pt/C, respectively. This work provides important insights into the structural design, performance optimization, and cost reduction to promote the practical applications of liquid fuel cells.

Gold-Copper Aerogels with Intriguing Surface Electronic Modulation as Highly Active and Stable Electrocatalysts for Oxygen Reduction and Borohydride Oxidation.

We, for the first time, report the successful synthesis of self-assembled AuCu aerogels by a one-pot kinetically controlled approach. A startling electronic modulation effect of Cu on Au was observed across the entire alloy composition range, for which the optimal upshift of the d-band center for the highest activities was 0.24 eV. Owing to the combination of a nanoporous architecture and a robust electronic effect, the Au52 Cu48 aerogels exhibited better catalytic performance for the oxygen reduction reaction (ORR) and the direct borohydride oxidation reaction (BOR) than commercial Pt/C catalysts. The specific and mass ORR activities were 4.5 and 6.3 times higher, respectively, on the Au52 Cu48 aerogels than on Pt/C with negligible activity decay even after 10 000 cycles and a duration of 40 000 s. For the BOR, the Au52 Cu48 aerogels also exhibited far better selectivity and activity than Pt/C. The new AuCu aerogels show great potential as a promising alternative for Pt-based catalysts in fuel cells.

Salvianolic acid B improves airway hyperresponsiveness by inhibiting MUC5AC overproduction associated with Erk1/2/P38 signaling.

Salvianolic acid B (SalB) is one of the main water-soluble composites from Chinese medicine Dansen (Radix miltiorrhiza). It is used for clinical treatment of various diseases including cardiovascular, lung, Liver, renal and cancers. However, the effects of SalB to allergy induced airway mucin hypersecretion, inflammation and hyperresponsiveness (AHR) remains not clear. Overproduction of airway MUC5AC is a central effector of inflammation that is strongly associated with AHR in asthmatic attack. In this study, we investigated the anti-asthmatic activity and mechanism of SalB in a murine model and human epithelial cells by monitoring changes in mucin expression and secretion, airway inflammation, AHR, and signaling pathways. SalB was administered by intragastric administration (i.g) daily for a week, starting at 21 days after sensitization of ovalbumin (OVA). All examinations were performed 24h after the last antigen challenge. We found that treatments with SalB significantly inhibited increase in the tracheobronchial secretion, glycosaminoglycan levels, interleukin (IL)-13, IL-4, and IL-5 cytokines mRNA and protein expression, and decrease in mucociliary clearance in lung tissues. Histological results demonstrated that SalB attenuated OVA-induced eosinophil infiltration, airway goblet cell hyperplasia, and MUC5AC and MUC5B mRNA and protein expression in lung tissues. SalB exhibited protective effects against AHR in OVA-challenged animals. In vitro, SalB significantly inhibited IL-13-induced MUC5AC and MUC5B mRNA and protein expression in human epithelial cells. These effects were blocked by SalB by downregulating the Erk1/2 and P38 signaling pathways. Taken together, these data indicate that treatment with SalB may improve AHR by inhibiting MUC5AC overproduction.

Soluble epoxide hydrolase inhibitor AUDA decreases bleomycin-induced pulmonary toxicity in mice by inhibiting the p38/Smad3 pathways.

Bleomycin (BLM) has potent tumor cell-killing properties that have given it an important place in cancer chemotherapy, but pulmonary toxicity is its major adverse effect. Soluble epoxide hydrolase (sEH) inhibitors have been reported to have protective effects in fibrosis models, but the effects of AUDA, an sEH inhibitor of BLM-induced pulmonary toxicity and fibrosis, remain to be researched. In this study, we assessed the effects of AUDA on the BLM-induced pulmonary fibrosis in a mouse model, and transforming growth factor (TGF)-ß1-induced epithelial proliferation and epithelial-mesenchymal transition (EMT) in vitro by monitoring changes in pulmonary function, inflammatory response, fibrotic remodeling, and signaling pathways. AUDA was administered by intragastric administration (i.g) daily for three weeks, starting at seven days after intratracheal instillation of BLM. All examinations were performed 24h after the last i.g. In vivo, AUDA significantly improved BLM-induced decline in lung function and body weight, and inhibited inflammatory cell accumulation and the mRNA and protein expression of interleukin (IL)-1ß, TGF-ß1, and matrix metalloproteinase 9 (MMP-9) in lung tissue. Moreover, AUDA attenuated BLM-induced deposition of collagen fibers, destruction of alveolar structures, and pulmonary parenchyma. Additionally, AUDA regulated the expression of α-smooth muscle actin (α-SMA) and E-cadherin by inhibiting the Smad3/p38 signaling pathway. In vitro, AUDA significantly inhibited TGF-ß1-induced epithelial cells and fibroblast proliferation, reduced sEH expression and α-SMA expression, and increased epoxyeicosatrienoic acid (EET) levels and E-cadherin expression in epithelial cells. These effects were blocked by AUDA by downregulating the Smad3 and p38 signaling pathways. Taken together, these data indicate that treatment with sEH inhibitors may improve BLM-induced pulmonary toxicity.

Ag-Cu nanoalloyed film as a high-performance cathode electrocatalytic material for zinc-air battery.

A novel Ag50Cu50 film electrocatalyst for oxygen reduction reaction (ORR) was prepared by pulsed laser deposition (PLD) method. The electrocatalyst actually is Ag-Cu alloyed nanoparticles embedded in amorphous Cu film, based on transmission electron microscopy (TEM) characterization. The rotating disk electrode (RDE) measurements provide evidence that the ORR proceed via a four-electron pathway on the electrocatalysts in alkaline solution. And it is much more efficient than pure Ag catalyst. The catalytic layer has maximum power density of 67 mW cm(-2) and an acceptable cell voltage at 0.863 V when current densities increased up to 100 mA cm(-2) in the Ag50Cu50-based primary zinc-air battery. The resulting rechargeable zinc-air battery exhibits low charge-discharge voltage polarization of 1.1 V at 20 mAcm(-2) and high durability over 100 cycles in natural air.

Silver-Copper Nanoalloy Catalyst Layer for Bifunctional Air Electrodes in Alkaline Media.

A carbon-free and binder-free catalyst layer composed of a Ag-Cu nanoalloy on Ni foam was used as the air cathode in a zinc-air battery for the first time. The Ag-Cu catalyst was prepared using pulsed laser deposition. The structures of the catalysts were found to consist of crystalline Ag-Cu nanoalloy particles with an average size of 2.58 nm embedded in amorphous Cu films. As observed in the X-ray photoelectron spectra, the Ag 3d core levels shifted to higher binding energies, whereas the Cu 2p core levels shifted to lower binding energies, indicating alloying of the silver and copper. Rotating disk electrode measurements indicated that the oxygen reduction reaction (ORR) proceeded through a four-electron pathway on the Ag50Cu50 and Ag90Cu10 nanoalloy catalysts in alkaline solution. Moreover, the catalytic activity of Ag50Cu50 in the ORR is more efficient than that of Ag90Cu10. By performing charge and discharge cycling measurements, the Ag50Cu50 catalyst layer was confirmed to have a maximum power density of approximately 86.3 mW cm(-2) and an acceptable cell voltage at 0.863 V for current densities up to 100 mA cm(-2) in primary zinc-air batteries. In addition, a round-trip efficiency of approximately 50% at a current density of 20 mA cm(-2) was also obtained in the test.

Integrated systems toxicology approaches identified the possible involvement of ABC transporters pathway in erythromycin estolate-induced liver injury in rat.

Erythromycin estolate (EE), a macrolide antibiotic, has caused hepatotoxicity both in human and experimental animals. The objective of this study was to integrate general toxicology, transcriptomics, and metabonomics approaches to determine the mechanisms of EE-induced liver injury. Histopathological examinations unveiled dose-dependent hydropicdegenerationof hepatocytes after EE administration. Further biochemical analysis of treated rats confirmed that cholestasis and oxidative stress were induced by EE treatments. Microarray analysis of the livers from EE-treated rats showed that differentially expressed genes were enriched in the ABC transporters, cell cycle, and p53 signaling pathways. Metabonomics analysis revealed that EE exposure could lead to disturbances in energy metabolism, amino acid metabolism, lipid metabolism, and nucleotide metabolism, which may be attributable to EE toxicological effects on the liver through oxidative stress. 5-Oxoproline may be used as a biomarker of EE-induced liver injury. More importantly, the integrated analysis of transcriptomics and metabonomics datasets demonstrated that the induction of ABC transporters pathway severed as an anti-cholestatic adaptive mechanism in EE-induced cholestasis. In addition, EE-induced liver injury was also related to alteration in glycogen and sucrose metabolism, arachidonic acid metabolism, and linoleic acid metabolism pathways.