Hydrolysis-Induced Cu2O Networks and the Triggered Peroxidase-Mimic Activity by Cr6+ under Neutral Conditions.

The current small-scale synthesis and relatively large size of Cu2O have limited its practical applications. Herein, we developed a hydrolysis strategy to prepare phase-pure Cu2O networks composed of small granules (ca. 25 nm) on a gram scale. The preparation involves in situ hydrolyzing the Hx[CuxCl2x] complexes prereduced in N,N'-dimethylformamide (DMF). The DMF-soluble Hx[CuxCl2x] complexes are critical for the homogeneous nucleation of CuCl seeds and subsequent hydrolysis, allowing for separate control over the nucleation and growth stages to regulate the formation of Cu2O networks. The novel Cu2O networks possess numerous exposed active sites and hierarchical porosities, conferring high catalytic activity and fast mass transfer capability. The inherent peroxidase-mimic activity of Cu2O is severely inhibited under neutral conditions but can be triggered by Cr6+, enabling the colorimetric assay of Cr6+ with the assistance of the oxidation-induced color change of 3,3',5,5'-tetramethylbenzidine. Through density functional theory calculation, we confirmed that the attachment of Cr6+ on the Cu2O surface reduced the dissociation energy of H2O2, enhancing the enzyme-mimic activity. The colorimetric detection method demonstrated a sensitive and specific assay capability for Cr6+ (LOD = 0.095 µM). Our work offers a straightforward protocol for novel design of metal or metal-based nanomaterials for nanozymes or other applications.

pH-Triggered Charge Reversible Fluorescent Probe for Simultaneous Imaging of Lipid Droplets and Nucleoli in Living Cells.

Cooperation between organelles is essential to maintain the normal functions of cells. Lipid droplets (LDs) and nucleoli, as important organelles, play an important role in the normal activities of cells. However, due to the lack of appropriate tools, in situ observation of the interaction between them has been rarely reported. In this work, taking into full consideration the pH and charge differences between LDs and nucleoli, a pH-triggered charge reversible fluorescent probe (LD-Nu) was constructed based on a cyclization-ring-opening mechanism. The in vitro pH titration experiment and 1H NMR showed that LD-Nu gradually transferred from the charged form to the electroneutral form with the increase of pH, and thus, the conjugate plane was reduced and its fluorescence blue-shifted. Most importantly, the physical contact between LDs and nucleoli was visualized for the first time. Meanwhile, the relationship between LDs and nucleoli was also further investigated, and the results showed that their interaction was more liable to be affected by the abnormality of LDs than those of nucleoli. Moreover, the cell imaging results displayed that the LDs both in the cytoplasm and nucleus were observed using the probe LD-Nu, and interestingly, the LDs in the cytoplasm were more susceptible to external stimuli than those in the nucleus. In a word, the probe LD-Nu can serve as a powerful tool for further exploration of the interaction mechanism between LDs and nucleoli in living cells.

Caffeic acid protects against atherosclerotic lesions and cognitive decline in ApoE-/- mice.

Caffeic acid has been indicated to benefit cholesterol balance, but the effect of pure caffeic acid on atherosclerosis in vivo has not been tested. Given that atherosclerosis and Alzheimer's disease share common features including distracted lipid balance and chronic inflammation, the concurrent effects of caffeic acid on atherosclerotic lesions and cognitive decline were explored here by using the ApoE-/- mice model. A two months' administration of 20 mg/kg caffeic acid or saline was given once two days intraperitoneally to 5-month-old female ApoE-/- mice. We found that the caffeic acid treatment reduced the atherosclerotic lesions in the whole aorta and aortic sinus of the resulting 7-month-old ApoE-/- mice by roughly 50%, compared with the saline control. Meanwhile, the cognitive decline of treated mice were significantly alleviated, as measured by Y-maze and Morris water maze tasks. A reduced accumulation of ß-amyloid in the hippocampus was also observed. These effects were associated with elevated serum HDL-c concentration, upregulated ABCA1 and ABCG1 mRNA levels, as well as decrease local inflammation and reduced levels of serum pro-inflammatory cytokines including TNF-α, IL-6 and MCP-1. These obtained results suggested the preventive and therapeutic potential of caffeic acid against atherosclerosis and Alzheimer's disease during aging.

The benzoate plant metabolite ethyl gallate prevents cellular- and vascular-lipid accumulation in experimental models of atherosclerosis.

Ethyl gallate (EG) is a well-known constituent of medicinal plants, but its effects on atherosclerosis development are not clear. In the present study, the anti-atherosclerosis effects of EG and the underlying mechanisms were explored using macrophage cultures, zebrafish and apolipoprotein (apo) E deficient mice. Treatment of macrophages with EG (20 µM) enhanced cellular cholesterol efflux to HDL, and reduced net lipid accumulation in response to oxidized LDL. Secretion of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) from activated macrophages was also blunted by EG. Fluorescence imaging techniques revealed EG feeding of zebrafish reduced vascular lipid accumulation and inflammatory responses in vivo. Similar results were obtained in apoE-/- mice 6.5 months of age, where plaque lesions and monocyte infiltration into the artery wall were reduced by 70% and 42%, respectively, after just 6 weeks of injections with EG (20 mg/kg). HDL-cholesterol increased 2-fold, serum cholesterol efflux capacity increased by ∼30%, and the levels of MCP-1 and IL-6 were reduced with EG treatment of mice. These results suggest EG impedes early atherosclerosis development by reducing the lipid and macrophage-content of plaque. Underlying mechanisms appeared to involve HDL cholesterol efflux mechanisms and suppression of pro-inflammatory cytokine secretion.

Diversity of protease-producing bacteria in the soils of the South Shetland Islands, Antarctica.

Proteases secreted from bacteria into soil play a key role in the degradation of organic nitrogen, which is the first and, usually, the rate-limiting step of nitrogen cycling. However, the diversity of protease-producing bacteria and their excreted proteases in Antarctic soil have not yet been fully explored. Here we studied 20 soil samples from the South Shetland Islands, Antarctica and isolated 253 strains with protease activity. These protease-producing bacteria belonged to the phyla Bacteroidetes, Proteobacteria, Actinobacteria, Firmicutes, and Deinococcus-Thermus. Thhe predominant genera were Arthrobacter (14.9%), Chryseobacterium (14.5%), Flavobacterium (14.5%), and Pseudomonas (14.5%). Most of these bacteria secreted serine proteases and metalloproteases. There was quite a large distribution in activity as quantified by protease and inhibition assays. Only a few strains secreted aspartic and/or cysteine proteases. Together these data provided novel insight into the diversity and mechanism of organic nitrogen degradation in Antarctic soils by various proteases, which may have potential in new biotechnological applications.

[Short-term and long-term outcomes of tricuspid valve replacement in patients with left ventricular dysfunction].

Objective: To examine the short-term and long-term outcomes of tricuspid valve replacement (TVR) in patients with left ventricular dysfunction. Methods: The clinical data of 24 patients with left ventricular dysfunction who received TVR at Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University from November 1993 to August 2018 were consecutively enrolled. There were 14 males and 10 females,aged (41.9±13.2) years old (range: 19 to 66 years old). The preoperative ejection fraction was (42.9±6.4)% (range: 21% to 49%), while less than 35% in 3 patients. The scores of Charlson comorbidity index were as follows: 5 patients for 0, 6 patients for 1, 7 patients for 2, 1 patient for 3 and 5 patients for 4. The European system for cardiac operative risk evaluation (EuroSCORE) Ⅰ was 3.6±2.1 (range: 1 to 9). The EuroSCORE Ⅱ was (4.91±2.40)% (range: 1.58% to 11.60%). The model for end-staged liver disease score was 1.8±1.2 (range: 0.2 to 7.1). The simplified model for end-staged liver disease score was 5.6±2.5 (range: 1.5 to 13.4). Follow-up was conducted by clinic. The long-term survival rate was calculated by Kaplan-Meier survival curve. Results: In-hospital mortality was 16.7% (4/24), including 1 patient for multiple organ failure and 3 patients for low cardiac output syndrome (LCOS). One patient needed continuous renal replacement therapy and 6 patients suffered from LCOS. The follow-up time was 1 to 19 years, with a median of 8 years. During the follow-up period, 4 patients died, including 2 deaths for cardiogenic cause, 1 death for anticoagulant complications, and 1 death for lung cancer. The 1, 5 and 10-year survival rates were 76.2%, 71.4% and 64.9%, respectively. Conclusion: The short-term and long-term clinical outcomes of TVR in patients with left ventricular dysfunction are acceptable, but the mortality and morbidity are still high.

Deep Learning for Feynman's Path Integral in Strong-Field Time-Dependent Dynamics.

Feynman's path integral approach is to sum over all possible spatiotemporal paths to reproduce the quantum wave function and the corresponding time evolution, which has enormous potential to reveal quantum processes in the classical view. However, the complete characterization of the quantum wave function with infinite paths is a formidable challenge, which greatly limits the application potential, especially in the strong-field physics and attosecond science. Instead of brute-force tracking every path one by one, here we propose a deep-learning-performed strong-field Feynman's formulation with a preclassification scheme that can predict directly the final results only with data of initial conditions, so as to attack unsurmountable tasks by existing strong-field methods and explore new physics. Our results build a bridge between deep learning and strong-field physics through Feynman's path integral, which would boost applications of deep learning to study the ultrafast time-dependent dynamics in strong-field physics and attosecond science and shed new light on the quantum-classical correspondence.

Dismantling complex networks based on the principal eigenvalue of the adjacency matrix.

The connectivity of complex networks is usually determined by a small fraction of key nodes. Earlier works successfully identify an influential single node, yet have some problems for the case of multiple ones. In this paper, based on the matrix spectral theory, we propose the collective influence of multiple nodes. An interesting finding is that some traditionally influential nodes have strong internal coupling interactions that reduce their collective influence. We then propose a greedy algorithm to dismantle complex networks by optimizing the collective influence of multiple nodes. Experimental results show that our proposed method outperforms the state of the art methods in terms of the principal eigenvalue and the giant component of the remaining networks.

Tunable Electrochemical C-N versus N-N Bond Formation of Nitrogen-Centered Radicals Enabled by Dehydrogenative Dearomatization: Biological Applications.

Herein, an environmentally friendly electrochemical approach is reported that takes advantage of the captodative effect and delocalization effect to generate nitrogen-centered radicals (NCRs). By changing the reaction parameters of the electrode material and feedstock solubility, dearomatization enabled a selective dehydrogenative C-N versus N-N bond formation reaction. Hence, pyrido[1,2-a]benzimidazole and tetraarylhydrazine frameworks were prepared through a sustainable transition-metal- and exogenous oxidant-free strategy with broad generality. Bioactivity assays demonstrated that pyrido[1,2-a]benzimidazoles displayed antimicrobial activity and cytotoxicity against human cancer cells. Compound 21 exhibited good photochemical properties with a large Stokes shift (approximately 130 nm) and was successfully applied to subcellular imaging. A preliminary mechanism investigation and density functional theory (DFT) calculations revealed the possible reaction pathway.

Mechanistic Insight into the Binding and Swelling Functions of Prepeptidase C-Terminal (PPC) Domains from Various Bacterial Proteases.

The bacterial prepeptidase C-terminal (PPC) domain can be found in the C termini of a wide variety of proteases that are secreted by marine bacteria. However, the functions of these PPC domains remain unknown due to a lack of systematic research. Here, the binding and swelling abilities of eight PPC domains from six different proteases were compared systematically via scanning electron microscopy (SEM), enzyme assays, and fluorescence spectroscopy. These PPC domains all possess the ability to bind and swell insoluble collagen. PPC domains can expose collagen monomers but cannot disrupt the pyridinoline cross-links or unwind the collagen triple helix. This ability can play a synergistic role alongside collagenase in collagen hydrolysis. Site-directed mutagenesis of the PPC domain from Vibrio anguillarum showed that the conserved polar and aromatic residues Y6, D26, D28, Y30, W42, E53, C55, and Y65 and the hydrophobic residues V10, V18, and I57 played key roles in substrate binding. Molecular dynamic simulations were conducted to investigate the interactions between PPC domains and collagen. Most PPC domains have a similar mechanism for binding collagen, and the hydrophobic binding pocket of PPC domains may play an important role in collagen binding. This study sheds light on the substrate binding mechanisms of PPC domains and reveals a new function for the PPC domains of bacterial proteases in substrate degradation.IMPORTANCE Prepeptidase C-terminal (PPC) domains commonly exist in the C termini of marine bacterial proteases. Reports examining PPC have been limited, and its functions remain unclear. In this study, eight PPCs from six different bacteria were examined. Most of the PPCs possessed the ability to bind collagen, feathers, and chitin, and all PPCs could significantly swell insoluble collagen. PPCs can expose collagen monomers but cannot disrupt pyridinoline cross-links or unwind the collagen triple helix. This swelling ability may also play synergistic roles in collagen hydrolysis. Comparative structural analyses and the examination of PPC mutants revealed that the hydrophobic binding pockets of PPCs may play important roles in collagen binding. This study provides new insights into the functions and ecological significance of PPCs, and the molecular mechanism of the collagen binding of PPCs was clarified, which is beneficial for the protein engineering of highly active PPCs and collagenase in the pharmaceutical industry and of artificial biological materials.

Sampling-based box-covering algorithm for renormalization of networks.

Covering a network with minimum number of boxes is critical for using the renormalization technique to explore the network configuration space in a multiscale fashion. Here, we propose a versatile methodology composed of flexible representation and sampling of boxes, which have so far received scant attention, and the strategy of selecting boxes to cover the network. It is exemplified via random box sampling strategies and greedy methods to select boxes. We show that the key to substantially reduce the number of boxes is to give the selection priority to those boxes containing nodes that are not included in boxes bigger than themselves. Our algorithm achieves the improvement of diminishing the number of boxes amounting to nearly 25% compared with these well known algorithms.

Flavobacterium phocarum sp. nov., isolated from soils of a seal habitat in Antarctica.

A Gram-stain-negative, yellow-pigmented, non-flagellated, gliding, rod-shaped, oxidase-negative and catalase-positive bacterium, designated SE14T, was isolated from soil on King George Island, South Shetland Islands, Antarctica. Strain SE14T grew at 4-25 °C (optimum, 20 °C), at pH 6.0-9.0 (optimum, pH 7.0-7.5) and with 0-3.0 % NaCl (optimum, 1.0-1.5 %), and could not produce flexirubin-type pigments. 16S rRNA gene sequence analysis showed the the isolate belonged to the genus Flavobacterium. Strain SE14T had the highest 16S rRNA gene sequence similarity to Flavobacterium antarcticum, F. tegetincola and F. degerlachei with 95.8, 95.5 and 95.2 %, respectively. The strain SE14T consisted of a clade with Flavobacteriumnoncentrifugens (16S rRNA gene sequence similarity 94.9 %) and F. qiangtangense (16S rRNA gene sequence similarity 94.2 %) and simultaneously formed a distinct phyletic lineage in the neighbour-joining phylogenetic tree. Polar lipids of the strain included phosphatidylethanolamine and four unidentified aminolipids. Strain SE14T contained anteiso-C15 : 0, iso-C15 : 0 and a mixture of iso-C15 : 0 2-OH and/or C16 : 1ω7c as the main fatty acids, and the only respiratory quinone was menaquinone-6. The genomic DNA G+C content was 42.3 mol%. The polyphasic taxonomic study revealed that strain SE14T belongs to a novel species within the genus Flavobacterium , and the name Flavobacterium phocarum sp. nov. is proposed. The type strain is SE14T (=CCTCC AB 2017225T=KCTC 52612T).

Neptunicoccus sediminis gen. nov., sp. nov., a member of the family Rhodobacteraceae isolated from the Yellow Sea.

A novel Gram-stain-negative bacterium, designated strain CY02T, was isolated from sediment of the Yellow Sea. Cells of CY02T were aerobic, coccus or short rods. Growth occurred at 5-42 °C (optimum, 35 °C), pH 6-10 (optimum, 8.0) and 0.5-9.0 % NaCl (optimum, 1.5-3.0 %). Phylogenetic analysis of 16S rRNA gene sequences revealed that CY02T was a member of the family Rhodobacteraceae and exhibited less than 95 % sequence similarities with the closely related type strains of the family Rhodobacteraceae. The genomic DNA G+C content of CY02T was 57.5 mol%. The major respiratory quinone was ubiquinone-10 (Q-10). The polar lipids consisted of phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, three unidentified lipids, one unidentified phospholipid and one unidentified aminolipid. The predominant cellular fatty acids were C18 : 1ω7c (57.6 %), 11-methyl C18 : 1ω7c (22.8 %) and C16 : 0 (10.6 %). Based on the results of morphological, physiological, biochemical, chemotaxonomic, genotypic and phylogenetic analyses, strain CY02T represents a novel species of a novel genus of the family Rhodobacteraceae, for which the name Neptunicoccus sediminis gen. nov., sp. nov. is proposed. The type strain of Neptunicoccus sediminis is CY02T (=CCTCC AB 2015430T=KCTC 42985T=NBRC 111872T=MCCC 1K03518).

Analytical connection between thresholds and immunization strategies of SIS model in random networks.

Devising effective strategies for hindering the propagation of viruses and protecting the population against epidemics is critical for public security and health. Despite a number of studies based on the susceptible-infected-susceptible (SIS) model devoted to this topic, we still lack a general framework to compare different immunization strategies in completely random networks. Here, we address this problem by suggesting a novel method based on heterogeneous mean-field theory for the SIS model. Our method builds the relationship between the thresholds and different immunization strategies in completely random networks. Besides, we provide an analytical argument that the targeted large-degree strategy achieves the best performance in random networks with arbitrary degree distribution. Moreover, the experimental results demonstrate the effectiveness of the proposed method in both artificial and real-world networks.

The Middle-Income Trap and the Coping Strategies From Network-Based Perspectives.

When a developing country reaches a relatively average income level, it often stops growing further and its income does not improve. This is known as the middle-income trap. How to overcome this trap is a longstanding problem for developing countries, and has been studied in various research fields. In this work, we use the Fitness-Complexity method (FCM) to analyze the common characteristics of the countries that successfully get through the middle-income trap, and show the origin of the middle-income trap based on the international trade network. In the analysis, a novel method is proposed to characterize the interdependency between products. The results show that some middle-complexity products depend much on each other, which indicates that developing countries should focus on them simultaneously, implying high difficulty to escape the middle-income trap. To tackle the middle-income trap, developing countries should learn experiences from developed countries that share similar development history. we then design an effective method to evaluate the similarity between countries and recommend developed countries to a certain developing country. The effectiveness of our method is validated in the international trade network.

Economic Complexity Based Recommendation Enhance the Efficiency of the Belt and Road Initiative.

The Belt and Road initiative (BRI) was announced in 2013 by the Chinese government. Its goal is to promote the cooperation between European and Asian countries, as well as enhancing the trust between members and unifying the market. Since its creation, more and more developing countries are joining the initiative. Based on the geographical location characteristics of the countries in this initiative, we propose an improvement of a popular recommendation algorithm that includes geographic location information. This recommendation algorithm is able to make suitable recommendations of products for countries in the BRI. Then, Fitness and Complexity metrics are used to evaluate the impact of the recommendation results and measure the country's competitiveness. The aim of this work is to provide countries' insights on the ideal development direction. By following the recommendations, the countries can quickly increase their international competitiveness.

Photobacterium proteolyticum sp. nov., a protease-producing bacterium isolated from ocean sediments of Laizhou Bay.

A protease-producing bacterial strain, 13-12T, was isolated from the ocean sediment of Laizhou Bay, PR China and systematically studied. The bacterium was Gram-stain negative, non spore-forming rods, which were motile with two flagella. It was positive for oxidase, the hydrolysis of starch, agar and gelatin, and for nitrate reduction. It was negative for catalase, esterase and the degradation of CM-cellulose. Optimum growth was observed at 28 °C, pH 6.5-7.0 and in the presence of 2-3 % (w/v) NaCl. Phylogenetic analysis of the 16S rRNA gene, and whole genome data, affiliated it to the genus Photobacterium. It was most closely related to Photobacterium jeanii R-40508T (96.7 % 16S rRNA gene similarity). Strain 13-12T was found to have less than 86.1 % similarities with the type strains of its most closely related species in multi-locus sequence analysis, less than 75.2 % using genome average nucleotide identities (ANI), and less than 18.5 % in DNA-DNA relatedness studies. Q8 was the predominant respiratory menaquinone. Phosphatidylethanolamine, phosphoaminolipid and phospholipid were the major polar phospholipids and summed feature 3 (48.2 %), C16 : 0 (18.4 %) and C18 : 1ω5c (14.1 %) the major fatty acids. The combined phenotypic, phylogenetic, genomic and chemotaxonomic data support this strain representing a novel species of the genus Photobacterium, for which the name Photobacterium proteolyticum sp. nov. is proposed, with 13-12T (=KCTC 42764T=CGMCC 1.14970) as the type strain. The genome size of 13-12T is 6.2 Mbp, comprising 5806 predicted genes and the DNA G+C content is 47.9 mol%.

Flavobacterium ardleyense sp. nov., isolated from Antarctic soil.

A Gram-stain-negative, aerobic, yellow-pigmented, non-flagellated, non-gliding, rod-like, oxidase- and catalase-positive bacterium, designated A2-1T, was isolated from soil on Ardley Island, South Shetland Islands, Antarctica. Strain A2-1T grew at 4-22 °C (optimum, 10 °C), at pH 6.0-8.0 (optimum, pH 6.5) and with 0-1.5 % NaCl (optimum, 0.5 %), but could not produce flexirubin-type pigments. 16S rRNA gene sequence analysis showed that the isolates belonged to the genus Flavobacterium. Strain A2-1T had the highest 16S rRNA gene sequence similarity to Flavobacterium cucumis, F. ahnfeltiae and F. cheniae with 95.7, 95.6 and 95.4 %, respectively. The strain A2-1T consisted of a clade with F. cucumis and F. cheniae and simultaneously formed a distinct phyletic lineage in the neighbour-joining phylogenetic tree. Polar lipids of the strain included phosphatidylethanolamine (PE), four unidentified aminolipids and one unidentified lipid. The strain A2-1T contained anteiso-C15 : 0 (20.2 %), iso-C15 : 0 (16.2 %) and C15 : 1 G (11.0 %) as the main fatty acids and the only respiratory quinone was menaquinone MK-6. The genomic DNA G+C content was 34.0 mol%. The polyphasic taxonomic study revealed that the strain A2-1T belongs to a novel species within the genus Flavobacterium and the name Flavobacterium ardleyense sp. nov. is proposed. The type strain is A2-1T (=CCTCC AB 2017157T=KCTC 52644T).

Euzebyella marina sp. nov., isolated from seawater.

A Gram-stain-negative, aerobic, yellow-pigmented, non-flagellated, non-gliding, oxidase- and catalase-positive bacterium, designated CY01T, was isolated from seawater of the Yellow Sea. CY01T grew at 15-37 °C (optimum, 30 °C), pH 5-8 (optimum, 6.5-7.5) and with 0.5-12 % (w/v) NaCl (optimum, 0.5-3.5 %). It could not produce flexirubin-type pigment or reduce nitrate to nitrite. CY01T showed the highest 16S rRNA gene sequence similarity to the type strain of Euzebyella saccharophila (97.0 %) and clustered tightly with the species of the genus Euzebyella in the phylogenetic trees based on the 16S rRNA gene sequences. The major cellular fatty acids of CY01T were iso-C15 : 0, iso-C15 : 1G and iso-C17 : 0 3-OH and the major respiratory quinone was menaquinone MK-6. Polar lipids included phosphatidylethanolamine (PE), four unidentified lipids and one unidentified aminolipid. The genomic DNA G+C content was 38.2 mol%. Based on the results of the polyphasic characterization of CY01T, it represents a novel species of the genus Euzebyella, for which the name Euzebyella marina sp. nov. is proposed. The type strain is CY01T (=CCTCC AB 2014348T=KCTC 42440T).

Simultaneous determination of epalrestat and puerarin in rat plasma by UHPLC-MS/MS: Application to their pharmacokinetic interaction study.

In the present study, a simple, rapid and reliable ultrahigh-performance liquid chromatography-tandem mass spectrometric (UHPLC-MS/MS) method was developed and validated to determine simultaneously epalrestat (EPA) and puerarin (PUE) in rat plasma for evaluation of the pharmacokinetic interaction of these two drugs. Both the analytes and glipizide (internal standard, IS) were extracted using a protein precipitation method. The separation was performed on a C18 reversed phase column using acetonitrile and 5 mmol/L ammonium acetate in water as the mobile phase with a gradient elution program. The analytes, including IS, were quantified with multiple reaction monitoring under negative ionization mode. The optimized mass transition ion pairs (m/z) were 318.1 → 274.0 for EPA, 415.1 → 266.9 for PUE and 444.2 → 166.9 for IS. The linear calibration curves for EPA and PUE were obtained in the concentration ranges of 10-4167 and 20-8333 ng/mL, respectively (r > 0.99). The current method was successfully applied for the pharmacokinetic interaction study in rats following administration of EPA and PUE alone or co-administration (EPA 15 mg/kg, oral; PUE 30 mg/kg, intravenous). The results showed that the combination of EPA and PUE could increase t1/2 of EPA and reduce Tmax of EPA. These changes indicated that EPA and PUE might cause drug-drug interactions when co-administrated.