Synthesis and Characterization of High-Purity, High-Entropy Diboride Ceramic Powders by a Liquid Phase Method.

A nano-dual-phase powder with ultra-fine grain size was synthesized by the liquid precursor method at 1200 °C. A series of single-phase high-entropy ceramic powders ((Ti, Zr, Hf, Nb)B2, (Ti, Zr, Hf, Nb, Ta)B2, (Ti, Zr, Hf, Nb, Mo)B2, (Ti, Zr, Hf, Nb, Ta, Mo)B2) with high purity (C content less than 0.9 wt% and O content less than 0.7 wt%) and ultrafine (average grain sizes of 340-570 nm) were successfully synthesized at 1800 °C. The sample of (TiZrHfNbTa)B2 exhibited a hexagonal close-packed (HCP) structure, and the metal elements were uniformly distributed at the nanoscale, microscale, and macroscale. This method did not apply to the preparation of all high-entropy ceramic powders and was unfavorable for the formation of single-phase high-entropy borides when the size difference factor exceeded 3.9%. The present work provides a guide for the development of ceramic-based composites through precursor impregnation pyrolysis.

Biosynthetic Pathways and Functions of Indole-3-Acetic Acid in Microorganisms.

Indole-3-acetic acid (IAA) belongs to the family of auxin indole derivatives. IAA regulates almost all aspects of plant growth and development, and is one of the most important plant hormones. In microorganisms too, IAA plays an important role in growth, development, and even plant interaction. Therefore, mechanism studies on the biosynthesis and functions of IAA in microorganisms can promote the production and utilization of IAA in agriculture. This mini-review mainly summarizes the biosynthesis pathways that have been reported in microorganisms, including the indole-3-acetamide pathway, indole-3-pyruvate pathway, tryptamine pathway, indole-3-acetonitrile pathway, tryptophan side chain oxidase pathway, and non-tryptophan dependent pathway. Some pathways interact with each other through common key genes to constitute a network of IAA biosynthesis. In addition, functional studies of IAA in microorganisms, divided into three categories, have also been summarized: the effects on microorganisms, the virulence on plants, and the beneficial impacts on plants.

The Novel Effector Ue943 Is Essential for Host Plant Colonization by Ustilago esculenta.

The smut fungus Ustilago esculenta obligately parasitizes Zizania latifolia and induces smut galls at the stem tips of host plants. Previous research identified a putative secreted protein, Ue943, which is required for the biotrophic phase of U. esculenta but not for the saprophytic phase. Here, we studied the role of Ue943 during the infection process. Conserved homologs of Ue943 were found in smut fungi. Ue943 can be secreted by U. esculenta and localized to the biotrophic interface between fungi and plants. It is required at the early stage of colonization. The Ue943 deletion mutant caused reactive oxygen species (ROS) production and callose deposition in the host plant at 1 and 5 days post inoculation, which led to failed colonization. The virulence deficiency was restored by overexpressing gene Ue943 or Ue943:GFP. Transcriptome analysis further showed a series of changes in plant hormones following ROS production when the host plant was exposed to ΔUe943. We hypothesize that Ue943 might be responsible for ROS suppression or avoidance of recognition by the plant immune system. The mechanism underlying Ue943 requires further study to provide more insights into the virulence of smut fungi.

Numerical and Field Investigations of Acoustic Emission Laws of Coal Fracture under Hydro-Mechanical Coupling Loading.

Taking coal under hydro-mechanical coupling as the research object, the discrete element software PFC3D (particle flow code) was used to analyze the relationships among the force, acoustic emission (AE), and energy during coal fracture. Based on the moment tensor (MT) inversion, we revealed the AE event distribution and source type during crack initiation and propagation until the final failure of coal. Meanwhile, we examined the relationships among the stress, number and type of cracks, magnitude, KE, and b value of AE under different water and confining pressures. The results show that the numerical simulation can effectively determine the microscopic damage mechanism of coal under different conditions. Moreover, the rupture type of the numerical simulation is consistent with the field investigations, which verifies the rationality of the simulation. These research results can provide reference for safety production evaluation of water inrush mines.

Hapten designs based on aldicarb for the development of a colloidal gold immunochromatographic quantitative test strip.

The common carbamate insecticide aldicarb is considered one of the most acutely toxic pesticides. Herein, rational design was used to synthesize two haptens with spacers of different carbon chain lengths. The haptens were then used to immunize mice. The antibodies obtained were evaluated systematically, and a colloidal gold immunochromatographic strip was developed based on an anti-aldicarb monoclonal antibody. The 50% inhibition concentration and linear range of anti-aldicarb monoclonal antibody immunized with Hapten 1 were 0.432 ng/mL and 0.106-1.757 ng/mL, respectively. The cross-reactivities for analogs of aldicarb were all <1%. The limit of detection of the colloidal gold immunochromatographic strip was 30 µg/kg, and the average recoveries of aldicarb ranged from 80.4 to 110.5% in spiked samples. In the analysis of spiked samples, the test strip could accurately identify positive samples detected by the instrumental method in the GB 23200.112-2018 standard but produced some false positives for negative samples. This assay provides a rapid and accurate preliminary screening method for the determination of aldicarb in agricultural products and environments.

Multimodal imaging distribution assessment of a liposomal antibiotic in an infectious disease model.

Liposomes are promising targeted drug delivery systems with the potential to improve the efficacy and safety profile of certain classes of drugs. Though attractive, there are unique analytical challenges associated with the development of liposomal drugs including human dose prediction given these are multi-component drug delivery systems. In this study, we developed a multimodal imaging approach to provide a comprehensive distribution assessment for an antibacterial drug, GSK2485680, delivered as a liposomal formulation (Lipo680) in a mouse thigh model of bacterial infection to support human dose prediction. Positron emission tomography (PET) imaging was used to track the in vivo biodistribution of Lipo680 over 48 h post-injection providing a clear assessment of the uptake in various tissues and, importantly, the selective accumulation at the site of infection. In addition, a pharmacokinetic model was created to evaluate the kinetics of Lipo680 in different tissues. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) was then used to quantify the distribution of GSK2485680 and to qualitatively assess the distribution of a liposomal lipid throughout sections of infected and non-infected hindlimb tissues at high spatial resolution. Through the combination of both PET and MALDI IMS, we observed excellent correlation between the Lipo680-radionuclide signal detected by PET with the GSK2485680 and lipid component signals detected by MALDI IMS. This multimodal translational method can reduce drug attrition by generating comprehensive biodistribution profiles of drug delivery systems to provide mechanistic insight and elucidate safety concerns. Liposomal formulations have potential to deliver therapeutics across a broad array of different indications, and this work serves as a template to aid in delivering future liposomal drugs to the clinic.

Quantum-Dot-Bead-Based Fluorescence-Linked Immunosorbent Assay for Sensitive Detection of Cry2A Toxin in Cereals Using Nanobodies.

In this study, a quantum-dot-bead (QB)-based fluorescence-linked immunosorbent assay (FLISA) using nanobodies was established for sensitive determination of the Cry2A toxin in cereal. QBs were used as the fluorescent probe and conjugated with a Cry2A polyclonal antibody. An anti-Cry2A nanobody P2 was expressed and used as the capture antibody. The results revealed that the low detection limit of the developed QB-FLISA was 0.41 ng/mL, which had a 19-times higher sensitivity than the traditional colorimetric ELISA. The proposed assay exhibited a high specificity for the Cry2A toxin, and it had no evident cross-reactions with other Cry toxins. The recoveries of Cry2A from the spiked cereal sample ranged from 86.6-117.3%, with a coefficient of variation lower than 9%. Moreover, sample analysis results of the QB-FLISA and commercial ELISA kit correlated well with each other. These results indicated that the developed QB-FLISA provides a potential approach for the sensitive determination of the Cry2A toxin in cereals.

Transcriptome Comparison between Two Strains of Ustilago esculenta during the Mating.

Ustilago esculenta is a smut fungus that obligately infects Zizania latifolia and stimulates tissue swelling to form galls. Unlike T-type, MT-type U. esculenta can only proliferate within plant tissues and infect the offspring of their host. Production of telispores, haploid life, and plant cuticle penetration are not essential for it, which may lead to the degeneration in these processes. Transcriptome changes during the mating of T- and MT-type U. esculenta were studied. The functions of several secreted proteins were further confirmed by knock-out mutants. Our results showed that MT-type U. esculenta can receive environmental signals in mating and circumstance sensing as T-type does. However, MT-type U. esculenta takes a longer time for conjunction tube formation and cytoplasmic fusion. A large number of genes encoding secreted proteins are enriched in the purple co-expression module. They are significantly up-regulated in the late stage of mating in T-type U. esculenta, indicating their relationship with infecting. The knock-out of g6161 (xylanase) resulted in an attenuated symptom. The knock-out of g943 or g4344 (function unidentified) completely blocked the infection at an early stage. This study provides a comprehensive comparison between T- and MT-type during mating and identifies two candidate effectors for further study.

In Vitro and In Vivo Activities, Absorption, Tissue Distribution, and Excretion of OBP-4, a Potential Anti-Clostridioides difficile Agent.

Clostridioides difficile infection (CDI) is considered a major concern of the health care system globally, with an increasing need for alternative therapies. OBP-4, a new oxazolidinone-fluoroquinolone hybrid with excellent in vitro activities and good safety, shows promising features as an antibacterial agent. Here, we further evaluated the in vitro and in vivo activities of OBP-4 against C. difficile and its absorption (A), distribution (D), and excretion (E) profiles in rats. In vitro assays indicated that OBP-4 was active against all tested C. difficile strains, with MICs ranging from 0.25 to 1 mg/liter. In addition, OBP-4 showed complete inhibition of spore formation at 0.5× MIC. In the mouse model of CDI, 5-day oral treatment with OBP-4 provided complete protection from death and CDI recurrence in infected mice. However, cadazolid (CZD) and vancomycin (VAN) showed less protection of infected mice than did OBP-4 in terms of diarrhea and weight loss, especially VAN. Subsequently, ADE investigations of OBP-4 with a reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method showed extremely low systemic exposure and predominantly fecal excretion, resulting in a high local concentration of OBP-4 in the intestinal tract-the site of CDI. These results demonstrated that OBP-4 possesses good activity against C. difficile and favorable ADE characteristics for oral treatment of CDI, which support further development of OBP-4 as a potential anti-CDI agent.

Anticancer activity of safranal against colon carcinoma is due to induction of apoptosis and G2/M cell cycle arrest mediated by suppression of mTOR/PI3K/Akt pathway.

The Editors of JBUON issue an Expression of Concern to 'Anticancer activity of safranal against colon carcinoma is due to induction of apoptosis and G2/M cell cycle arrest mediated by suppression of mTOR/PI3K/Akt pathway', by Yibing Zhang, Yong Zhao, Jianyou Guo, Haifeng Cui, Sha Liu, JBUON 2018;23(3):574-578; PMID:30003721. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

An improved vegetation cover and management factor for RUSLE model in prediction of soil erosion.

Soil erosion and runoff of cultivated land will cause farmland to be degraded and the downstream to be contaminated, which has aroused extensive attention worldwide. The conventional soil loss prediction model revised universal soil loss equation (RUSLE) is capable of more significantly simulating and predicting the amount of soil loss, but this model often cannot achieve the satisfied prediction accuracy when the rainfall distribution of 1 year is significantly inconsistent with the annual distribution law. In this study, the 3-year field experiments were performed in Jilin, China. Besides, an improved revised universal soil loss equation (IRUSLE) was provided with a novel vegetation cover and management factor (C). It considered the interaction between rainfall distribution and normalized difference vegetation index (NDVI) by theoretical analysis and the genetic algorithm. It was reported that IRUSLE model can achieve more effective simulation result than RULSE model, as well as laying a theoretical basis for soil loss prediction.

Notoginsenoside R1 attenuates sevoflurane-induced neurotoxicity.

BACKGROUND: Sevoflurane, a volatile anesthetic, is known to induce widespread neuronal degeneration and apoptosis. Recently, the stress-inducible protein sestrin 2 and adenosine monophosphate-activated protein kinase (AMPK) have been found to regulate the levels of intracellular reactive oxygen species (ROS) and suppress oxidative stress. Notoginsenoside R1 (NGR1), a saponin isolated from Panax notoginseng, has been shown to exert neuroprotective effects. The effects of NGR1 against neurotoxicity induced by sevoflurane were assessed. METHODS: Sprague-Dawley rat pups on postnatal day 7 (PD7) were exposed to sevoflurane (3%) anesthesia for 6 h. NGR1 at doses of 12.5, 25, or 50 mg/kg body weight was orally administered to pups from PD2 to PD7. RESULTS: Pretreatment with NGR1 attenuated sevoflurane-induced generation of ROS and reduced apoptotic cell counts. Western blotting revealed decreased cleaved caspase 3 and Bad and Bax pro-apoptotic protein expression. NGR1 substantially upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression along with increased heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase-1 levels, suggesting Nrf2 signaling activation. Enhanced sestrin-2 and phosphorylated AMPK expression were noticed following NGR1 pretreatment. CONCLUSION: This study revealed the neuroprotective effects of NGR1 through effective suppression of apoptosis and ROS via regulation of apoptotic proteins and activation of Nrf2/HO-1 and sestrin 2/AMPK signaling cascades.

Functional Properties of the MAP Kinase UeKpp2 in Ustilago esculenta.

Ustilago esculenta undergoes an endophytic life cycle in Zizania latifolia. It induces the stem of its host to swell, forming the edible galls called jiaobai in China, which are the second most commonly cultivated aquatic vegetable in China. Z. latifolia raised for jiaobai can only reproduce asexually because the U. esculenta infection completely inhibits flowering. The infection and proliferation in the host plants during the formation of edible gall differ from those of conventional pathogens. Previous studies have shown a close relationship between mitogen-activated protein kinase (MAPK) and fungal pathogenesis. In this study, we explored the functional properties of the MAPK UeKpp2. Cross-species complementation assays were carried out, which indicated a functional complementation between the UeKpp2 of U. esculenta and the Kpp2 of Ustilago maydis. Next, UeKpp2 mutants of the UeT14 and the UeT55 sporidia background were generated; these showed an aberrant morphology of budding cells, and attenuated mating and filamentous growth in vitro, in the context of normal pathogenicity. Interestingly, we identified another protein kinase, UeUkc1, which acted downstream of UeKpp2 and may participate in the regulation of cell shape. We also found a defect of filamentous growth in UeKpp2 mutants that was not related to a defect of the induction of mating-type genes but was directly related to a defect in UeRbf1 induction. Overall, our results indicate an important role for UeKpp2 in U. esculenta that is slightly different from those reported for other smut fungi.

Carboxyl-Functionalized, Europium Nanoparticle-Based Fluorescent Immunochromatographic Assay for Sensitive Detection of Citrinin in Monascus Fermented Food.

A fluorescent immunochromatographic test strip (FICTS) based on the use of europium nanoparticles (EuNPs) was developed and applied to detect citrinin (CIT) in Monascus fermented food. The sensitivity of the immunoassay to detect CIT was greatly improved by the use of a specific monoclonal antibody to attach EuNPs to form a probe. Under optimum conditions, the visual detection limit was 2.5 ng/mL, and the detection limit of the instrument was 0.05 ng/mL. According to the results, the IC50 was 0.4 ng/mL. Matrix interference from various Monascus fermented foods was investigated in food sample detection. The immunosensor also demonstrated high recoveries (86.8-113.0%) and low relative standard deviations (RSDs) (1.8-15.3%) when testing spiked Monascus fermented food. The detection results of this method showed a good correlation (R2 > 0.98) with high-performance liquid chromatography (HPLC). The results showed that the FICTS method could be used as a rapid, sensitive method to detect CIT in Monascus fermented food.

Cloning and disruption of the UeArginase in Ustilago esculenta: evidence for a role of arginine in its dimorphic transition.

BACKGROUND: Ustilago esculenta, a typical dimorphic fungus could infect Zizania latifolia and induce host stem swollen to form an edible vegetable called Jiaobai in China. The strains differentiation especially in the mating ability and pathogenicity is closely related to different phenotypes of Jiaobai formed in the fields. Dimorphic switching, a tightly regulated processes, is essential for the pathogenetic development of dimorphic fungi. In responses to environment cues, dimorphic switching can be activated through two conserved cell signaling pathways-PKA and MAPK pathways. Previous study indicated that exogenous arginine could induce hyphal formation in several dimorphic fungi through hydrolysis by arginase, but inhibit the dimorphic transition of U. esculenta. We conducted this study to reveal the function of arginine on dimorphic transition of U. esculenta. RESULTS: In this study, we found that arginine, but not its anabolites, could slow down the dimorphic transition of U. esculenta proportionally to the concentration of arginine. Besides, UeArginase, predicated coding arginase in U. esculenta was cloned and characterized. UeArginase mutants could actually increase the content of endogenous arginine, and slow down the dimorphic transition on either nutritious rich or poor medium. Either adding exogenous arginine or UeArginase deletion lead to down regulated expressions of UePkaC, UePrf1, mfa1.2, mfa2.1, pra1 and pra2, along with an increased content of arginine during mating process. CONCLUSION: Results of this study indicated a direct role of arginine itself on the inhibition of dimorphic transition of U. esculenta, independent of its hydrolysis by UeArginase.

Structure-guided design of antibacterials that allosterically inhibit DNA gyrase.

A series of DNA gyrase inhibitors were designed based on the X-ray structure of a parent thiophene scaffold with the objective to improve biochemical and whole-cell antibacterial activity, while reducing cardiac ion channel activity. The binding mode and overall design hypothesis of one series was confirmed with a co-crystal structure with DNA gyrase. Although some analogs retained both biochemical activity and whole-cell antibacterial activity, we were unable to significantly improve the activity of the series and analogs retained activity against the cardiac ion channels, therefore we stopped optimization efforts.

Synthesis, Antibacterial Activities, Mode of Action and Acute Toxicity Studies of New Oxazolidinone-Fluoroquinolone Hybrids.

To combat bacterial resistance, a series of new oxazolidinone-fluoroquinolone hybrids have been synthesized and characterized. All synthetic hybrids were preliminarily evaluated for their in vitro antibacterial activities against 6 standard strains and 3 clinical isolates. The majority of hybrids displayed excellent activities against Gram-positive bacteria, but limited activities against Gram-negative bacteria. Hybrids OBP-4 and OBP-5 were found to be the most promising compounds. Further, in vitro antibacterial activities, mode of action and acute toxicity in mice of hybrids OBP-4 and OBP-5 were investigated. Hybrids OBP-4 and OBP-5 exhibited potent activities against Gram-positive bacteria, including drug-resistant strains. Correspondingly, studies on the mode of action of hybrids OBP-4 and OBP-5 indicated a strong inhibitory activity on protein synthesis by binding the active site of 50S subunit, but a weak inhibitory action on DNA synthesis. In addition, LD50 values of hybrids OBP-4 and OBP-5 in the acute oral toxicity were larger than 2000 mg/kg, suggesting a good safety profile.

Mating-type loci of Ustilago esculenta are essential for mating and development.

Ustilago esculenta is closely related to the smut fungus Ustilago maydis and, in an endophytic-like life in the plant Zizania latifolia, only infects host stems and causes swollen stems to form edible galls called Jiaobai in China. In order to study its different modes of invasion and sites of symptom development from other smut fungi at the molecular level, we first characterized the a and b mating-type loci of U. esculenta. The a loci contained three a mating-type alleles, encoding two pheromones and one pheromone receptor per allele. The pheromone/receptor system controlled the conjugation formation, the initial step of mating, in which each pheromone was specific for recognition by only one mating partner. In addition, there are at least three b alleles identified in U. esculenta, encoding two subunits of heterodimeric homeodomain transcription factors bE and bW, responsible for hyphal growth and invasiveness. Hyphal formation, elongation and invasion after mating of two compatible partners occurred, only when a heterodimer complex was formed by the bE and bW proteins derived from different alleles. We also demonstrated that even with only one paired pheromone-pheromone receptor, the active b locus heterodimer triggered hyphal growth and infection.

Alantolactone exhibits selective antitumor effects in HELA human cervical cancer cells by inhibiting cell migration and invasion, G2/M cell cycle arrest, mitochondrial mediated apoptosis and targeting Nf-kB signalling pathway.

PURPOSE: Cervical cancer is responsible for significant mortality and morbidity across the globe. Owing to the adverse effects of the currently used chemotherapy, research is directed to develop effective and safer chemotherapy for cervical cancer. This study was therefore designed to examine the effects of Alantolactone (AL) against a panel of human cervical cancer cells (HeLa, C4-1, MEK-180, C33A) and a normal cell line (HCerEPiC). METHODS: Cell viability was examined by WST-1 assay. Cell migration and invasion were examined by transwell assay. Cell cycle analysis was performed by flow cytometry. Apoptosis was detected by annexin V/propidium iodide (PI) and DAPI staining. Western blot analysis was used to examine protein expression. RESULTS: The results revealed that AL inhibits the growth of the all the cervical cancer cells in a concentration -dependent manner and exhibited the lowest IC50 of 15 µM against the HeLa cervical cancer cells. The anticancer effects of AL were due to induction of mitochondrial mediated apoptosis. AL caused enhancement in the expression of apoptosis regulatory proteins such as caspase 3 and Bax in cervical cancer cells. AL not only prompted the accumulation of the cervical cancer cells in the G2/M phase of the cell cycle but also inhibited the expressions of various cyclins. Transwell assay revealed that AL suppresses the migration and invasion of cervical cancer cells. Moreover AL could also block the NF-kB signalling pathway concentration-dependently. CONCLUSIONS: It is concluded that AL may serve as an important lead molecule for the development of therapy for cervical cancer.

Vasorelaxant effect of osthole on isolated thoracic aortic rings in rats.

OBJECTIVE: To investigate the effect of osthole on isolated thoracic aortic rings, and to determine the potential mechanism of action. METHODS: Thoracic aortas were isolated from Wistar rats, and were suspended in tissue organ chambers for vascular tension measurement. The effect of cumulative osthole (10－?, 10－?, 10－?, 10－?, and 10－? mol/L) on endothelium-intact and endothelium-denuded thoracic aortic rings pre-contracted with phenylephrine (PE, 10－? mol/L) or KCl (6 × 10－? mol/L) was recorded. Histomorphological changes of thoracic aorta were analyzed by hematoxylin-eosin. The effects of different osthole concentrations on endothelium-intact aortic rings, which were pre-inhibited with the non-selective nitric oxide synthase inhibitor L-Arg(NO2)-OMe·HCl (3 × 10－4 mol/L), endothelium-derived nitric oxide synthase inhibitor Nω-nitro-L-arginine (3 × 10－4 mol/L), guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-α] quinoxaline-1-one (10－5 mol/L), cyclooxygenase inhibitor indometacin (10－5 mol/L), and the Ca2+-activated potassium channel inhibitor tetraethylammonium nitrate (10－5 mol/L), and then contracted with PE, were examined. Aortic rings incubated with osthole (10－5 mol/L), phentolamine (10－5 mol/L), or verapamil (10－5 mol/L) in Ca2+-free Krebs-Henseleit solution (KHS) were stimulated with PE or KCl. RESULTS: There was a dose-dependent increase in vasorelaxation of isolated thoracic aortic rings (both with and without endothelium) with increasing osthole concentration. Hematoxylin-eosin staining showed that osthole significantly improved thoracic aorta ring morphology. Compared with the control group, there were also significant differences after incubation with L-Arg(NO2)-OMe·HCl, Nω-nitro-L-arginine, and 1H-[1,2,4] oxadiazolo [4,3-α] quinoxaline-1-one (P < 0.05 for all). The relaxation rate of the rings in the osthole group incubated with indometacin and tetraethylammonium nitrate were similar to controls. In Ca2+-free KHS, the PE-induced contraction was similar between the osthole (4.37% ± 0.41%) and control (4.21% ± 1.33%) groups. However, after cumulative CaCl2 (0.5, 1, 1.5, 2, 2.5, and 3 mmol/L), the Ca2+-induced contraction was significantly inhibited in the osthole and phentolamine groups compared with controls (P < 0.05). After cumulative CaCl2 was added to Ca2+-free KHS (high K+ concentration), the contraction rate was significantly higher than both of the control and the osthole groups (P < 0.05). The contraction rate in the osthole group was higher than the verapamil group (P < 0.05). CONCLUSION: Osthole has a vasorelaxant effect on isolated rat thoracic aortic rings, via inhibition of both receptor-operated and voltage-dependent Ca2+ channels in arterial smooth muscle, leading to decreased Ca2+ influx, and via inhibition of nitric oxide release on arterial endothelial cells.