Brønsted acid-mediated tandem cyclization of triarylphosphines and in situ generated ortho-alkynyl quinone methides: access to heterocyclic quaternary phosphonium salts.

Heterocyclic Quaternary Phosphonium Salts (HQPS) have emerged as promising chemicals for organic synthesis and medicinal chemistry. However, the present synthetic methodology of this type of compound is still limited. Here, we report a deconstructive reorganization strategy based on Brønsted acid-mediated tandem 1,4 addition/intramolecular cyclization of triphenylphosphine derivatives and in situ generated o-AQMs for the first time. This protocol provides a novel approach to heterocyclic quaternary phosphonium salts. The method also features a non-metal catalyst, mild reaction conditions, high efficiency and wide substrate scope. Moreover, a series of obtained heterocyclic phosphonium salts can be converted to isotopically labelled 2-benzofuran compounds directly by simple deuteration reactions.

Active fault tolerant tracking control of turbofan engine based on virtual actuator.

In this paper, an active fault-tolerant tracking control scheme for the turbofan engine under dynamic and simultaneous actuator faults and sensor faults under disturbances is proposed. First, based on the linear parameter-varying model of the turbofan engine, an H∞ state feedback nominal controller is designed so as to achieve rotor speed tracking control with adaptive gain scheduling characteristics at different working conditions for the turbofan engine. Next, for the control system with simultaneous multiplicative actuator faults and additive sensor faults, a virtual actuator based active fault-tolerant tracking control strategy is developed to reconfigure the system such that it can obtain the similar behavior to the fault-free system without modifying the nominal controller. Specifically, in addition to handle the actuator fault by the virtual actuator, the reconfigured controller adopts a feedforward control signal to compensate for the sensor fault. Besides, in order to guarantee the reconfigured system, a sufficiency criterion is proposed. Finally, simulations have been conducted on a twin-spool turbofan engine to verify the effectiveness of the strategy.

Alkaloid from Alstonia yunnanensis diels root against gastrointestinal cancer: Acetoxytabernosine inhibits apoptosis in hepatocellular carcinoma cells.

Liver cancer belongs to Gastrointestinal (GI) malignancies which is a common clinical disease, a thorny public health problem, and one of the major diseases that endanger human health. Molecules from natural products (NPs) or their derivatives play an increasingly important role in various chronic diseases such as GI cancers. The chemical composition of the Alstonia yunnanensis Diels roots was studied using silica column chromatography, gel chromatography, recrystallization, and HPLC, and the compounds were structurally identified by modern spectral analysis using mass spectrometry (MS) and nuclear magnetic resonance (1H-, 13C-, HMQC-, HMBC-, and 1H-1HCOSY-NMR), ultraviolet and visible spectrum (UV), and electronic Circular Dichroism (ECD). Acetoxytabernosine (AC), an indole alkaloid with antitumor activity, was isolated from Alstonia yunnanensis Diels root. The current study aimed to investigate the influence of AC on the cell proliferation of BEL-7402 and SMMC7721 and to elucidate the underlying mechanism. The absolute configuration of AC was calculated by ECD (electronic circular dichroism). The effects of AC on the viability of different tumor cell lines were studied by the SRB method. The death mode of human hepatoma cells caused by AC was studied by TUNEL cell apoptosis detection and AnnexinV-FITC/PI double staining image. Mitochondrial membrane potential was detected by JC-1. The effects of AC on the expression of apoptosis-related proteins (Caspase9, Caspase3, and Parp-1) in SMMC7721 and BEL-7402 cells were detected by western blot. It was found that the absolute configuration of AC is 19(s), 20(s)-Acetoxytabernosine. AC could induce apoptosis of SMMC7721 and BEL-7402, and block the replication of DNA in the G1 phase. Under the treatment of AC, the total protein expression of apoptosis-related proteins (Caspase9, Caspase3, and Parp-1) significantly decreased in SMMC7721 and BEL-7402. The results suggested that AC induced apoptosis through a caspase-dependent intrinsic pathway in SMMC7721 and BEL-7402, and natural product-based drug development is an important direction in antitumor drug discovery and research.

Abscisic acid modulates differential physiological and biochemical responses of roots, stems, and leaves in mung bean seedlings to cadmium stress.

Experiments were conducted to determine how exogenous abscisic acid (ABA) mediates the tolerance of plants to cadmium (Cd) exposure. Cd stress strongly reduced all the growth parameters of mung bean seedlings. Cd significantly increased ascorbate peroxidase (APX) and catalase (CAT) activities in roots and stems, and peroxidase (POD) activities in roots, stems, and leaves of mung bean seedlings. Cd caused remarkable increases in the levels of leaf chlorophyll and carotenoid, root polyphenols, and malondialdehyde (MDA) and proline in the three organs. However, Cd greatly decreased leaf CAT activity, root and leaf ascorbic acid (AsA) levels, and stem and leaf polyphenol levels. Foliar application of ABA partially alleviated Cd toxicity on the seedlings. ABA could restore most of the changed biochemical parameters caused by Cd, suggesting that ABA played roles in the protection of membrane lipid peroxidation and the modulation of antioxidative defense systems in response to Cd stress. Our results also implied the differential physiological and biochemical responsive patterns of roots, stems, and leaves to Cd and ABA in mung bean seedlings. The great changes in many biochemical parameters in roots suggested that roots were the first to be affected by Cd and play pivotal roles in response to Cd, especially in chelating Cd and reducing Cd absorption.

[Indicators of Groundwater Evolution Processes Based on Hydrochemistry and Environmental Isotopes: A Case Study of the Dongyuan Drinking Water Source Area in Ji'nan City].

The Dongyuan groundwater source area, which is the main drinking water source of Ji'nan City, is karst fissure water. To identify groundwater recharge sources, the influence of surface water, hydrochemical evolution, hydrochemical and isotopic components (2H and 18O) of groundwater and surface water samples collected from the Dongyuan groundwater source were investigated.The results showed that the hydrochemical characteristics of groundwater were similar, and the main ions were Ca2+, HCO3-, and SO42-. The groundwater, which suffered evaporation to varying degrees, was recharged mainly by precipitation. The hydrochemical composition of regional groundwater is mainly controlled by water-rock interactions, including dissolution/precipitation of carbonate minerals in the limestone aquifers and hydrolysis of silicates minerals in the quaternary aquifers, above the limestone aquifers. In some areas, groundwater was polluted by infiltration of river water. The main indicators of groundwater pollution that exceeded groundwater quality standards were total hardness, NO3-, NH4+, SO42-, Fe, and Mn.

Lewis Base-Catalyzed [4 + 3] Annulation of ortho-Quinone Methides and MBH Carbonates: Synthesis of Functionalized Benzo[ b]oxepines Bearing Oxindole Scaffolds.

A novel Lewis base-catalyzed [4 + 3] annulation process for the construction of benzo[ b]oxepine scaffolds has been developed. 1,4-Diazabicyclo[2.2.2]octane (DABCO) promotes the union of o-QMs and Morita-Baylis-Hillman carbonates in reasonable to excellent yields and good stereoselectivities (dr > 20:1). This straightforward, catalytic approach offers access to a variety of synthetically useful benzo[ b]oxepine derivatives bearing oxindole scaffolds containing all-carbon spiro-quaternary stereocenters.

Legacy and emerging contaminants in coastal surface sediments around Hainan Island in South China.

Emerging and legacy hydrophobic pollutants, including halogenated flame retardants (HFRs), organophosphorus FRs (OPFRs), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs), as well as polycyclic aromatic hydrocarbons (PAHs) were determined in coastal sediments of Hainan Island, southern China, where little information is known about their contamination. The HFRs were dominated by decabrominated diphenyl ethers (median = 1.32 ng/g) and novel decabromodiphenyl ethane (1.87 ng/g). HFR and PAH concentrations had similar spatial distributions, with higher levels in the river and near the estuary. The concentrations of ∑10OPFRs ranged from 0.74 to 60.0 ng/g (median = 15.3 ng/g), displaying a different spatial distribution. ∑DDTs and ß-HCH, with median concentrations of 1.41 and 3.44 ng/g respectively, were largely from historical inputs, but use of DDT still exists in Hainan. Principal component analysis revealed the associations between most of the pollutants (HFRs, OCPs, and PAHs) and perylene, indicating that terrestrial runoff plays a significant role in their presence in the coastal sediments. OPFRs had different emission sources or entry modes to the coastal ocean.

[Behavioral responses of Holotrichia oblita larvae to root exudates from three host plants]. / 华北大黑鳃金龟幼虫对3ç§å¯„ä¸»æ¤ç‰©æ ¹ç³»åˆ†æ³Œç‰©çš„è¶‹æ€§ååº”.

The larva of Holotrichia oblita is a serious soil pest that feed with plant roots in north China. To explore the effects of host root exudates on the larva could provide theoretical basis for the development of green prevention and control methods. In order to elucidate the behavioral responses of Holotrichia oblita larva to the roots of peanut, soybean and maize, an experiment was conducted using the Y-olfactometers with the air as control. The constituents of the root exudates from the three host plants were identified by the gas chromatography-mass spectrometer (GC-MS). The olfactory responses of H. oblita larvae to the main components were tested. The results showed that H. oblita larvae had a significant behavioral preference toward the roots of peanut, soybean and maize than the control. The GC-MS analysis showed that the main components of volatile compounds in the three plants had more than twenty compounds, with only three shared ones, which was glycerol, dodecanol, ethyl benzene. The results of the Y-olfactometers showed that at low concentrations (40 to 80 µg·mL-1), the number of insects attracted by compound 2-butenoic acid, methylsuccinic acid, myristic acid, acetic acid and phthalate was significantly higher than that of control. At the concentrations of 100 µg·mL-1, 200 µg·mL-1, compound tetradecane and hexadecane were more attractive to the larvae than the control. The compounds p-xylene, o-xylene, and palmitic acid glycerol were found to significantly induce the larva at the concentration of 300 µg·mL-1 and 500 µg·mL-1. In summary, the main components of plant root exudates had a significant luring effect on H. oblita larvae.

Acupoint Embedding of Polyglactin 910 Sutures in Patients with Chronic Pain due to Cervical Spondylotic Radiculopathy: A Multicenter, Randomized, Controlled Clinical Trial.

OBJECTIVE: We aimed to investigate the effectiveness of acupoint polyglactin 910 (PGLA) embedding in patients with cervical spondylotic radiculopathy (CSR). METHODS: A total of 102 CSR patients with neck and shoulder pain were recruited and assigned randomly into three groups: the sham acupoint embedding (SAE) group, the middle-layer acupoint PGLA embedding (MAPE) group, and the deep-layer acupoint PGLA embedding (DAPE) group. The primary outcomes were Visual Analog Scale (VAS) scores showing the analgesic effects of treatment. Secondary outcomes included clinical symptoms (evaluated by the Yasuhisa Tanaka 20 (YT-20) score and the neck disability index (NDI)) and patient health status (evaluated by the 36-item short-form survey (SF-36)) as reported in the trial. RESULTS: Compared with the SAE group, VAS scores were significantly reduced at 1, 2, 3, 4, and 10 weeks after the first treatment in both the DAPE and MAPE groups (P < 0.001). Moreover, there were statistically significant increases in the weekly YT-20 scores and significant reductions of the weekly NDI scores compared with baseline values in both the DAPE and MAPE groups (P < 0.001). Compared with baseline values, both the physical component summary (PCS) and the mental component summary scores of the SF-36 at 2, 3, 4, and 10 weeks were significantly higher in the DAPE and MAPE groups (P < 0.001). There were significant lower VAS scores (P < 0.01), higher PCS scores (P < 0.05) at 3 weeks, and lower NDI scores (P < 0.05) at 4 weeks in the DAPE group compared with the MAPE group. CONCLUSIONS: Both DAPE and MAPE showed significant and long-lasting effects on alleviating pain and improving clinical symptoms as well as quality of life in CSR patients with neck and shoulder pain. A more intense effect was seen in the DAPE group compared with the MAPE group.

Lewis Acid Catalyzed Tandem 1,4-Conjugate Addition/Cyclization of in Situ Generated Alkynyl o-Quinone Methides and Electron-Rich Phenols: Synthesis of Dioxabicyclo[3.3.1]nonane Skeletons.

A versatile Lewis acid catalyzed tandem cyclization of in situ generated alkynyl o-quinone methides ( o-AQMs) with electron-rich phenols has been developed on the basis of the mode involving an intermolecular 1,4-conjugate addition/6-endo cyclization/1,3-aryl shift/intramolecular 1,4-conjugate addition cascade. This reaction provides a new method for expeditious assembly of synthetically and biologically interesting tetracyclic bridged dioxabicyclo[3.3.1]nonane skeletons featuring a congested bridgehead oxa-quaternary stereocenter.

Metal-Free One-Pot Synthesis of 3-Phosphinoylbenzofurans via Phospha-Michael Addition/Cyclization of H-Phosphine Oxides and in Situ Generated ortho-Quinone Methides.

A novel metal-free one-pot protocol for the effective and efficient synthesis of 3-phosphinoylbenzofurans via a phospha-Michael addition/cyclization of H-phosphine oxides and in situ generated ortho-quinone methides is described. Based on the expeditious construction of C(sp2)-P bonds, asymmetric synthesis of optically pure 3-phosphinoylbenzofurans containing chiral P-stereogenic center has also been probed by using chiral RP-(-)-menthyl phenylphosphine oxide.

Diallyl disulfide suppresses epithelial-mesenchymal transition, invasion and proliferation by downregulation of LIMK1 in gastric cancer.

Diallyl disulfide (DADS) has been shown to have multi-targeted antitumor activities. We have previously discovered that it has a repressive effect on LIM kinase-1 (LIMK1) expression in gastric cancer MGC803 cells. This suggests that DADS may inhibit epithelial-mesenchymal transition (EMT) by downregulating LIMK1, resulting in the inhibition of invasion and growth in gastric cancer. In this study, we reveal that LIMK1 expression is correlated with tumor differentiation, invasion depth, clinical stage, lymph node metastasis, and poor prognosis. DADS downregulated the Rac1-Pak1/Rock1-LIMK1 pathway in MGC803 cells, as shown by decreased p-LIMK1 and p-cofilin1 levels, and suppressed cell migration and invasion. Knockdown and overexpression experiments performed in vitro demonstrated that downregulating LIMK1 with DADS resulted in restrained EMT that was coupled with decreased matrix metalloproteinase-9 (MMP-9) and increased tissue inhibitor of metalloproteinase-3 (TIMP-3) expression. In in vitro and in vivo experiments, the DADS-induced suppression of cell proliferation was enhanced and antagonized by the knockdown and overexpression of LIMK1, respectively. Similar results were observed for DADS-induced changes in the expression of vimentin, CD34, Ki-67, and E-cadherin in xenografted tumors. These results indicate that downregulation of LIMK1 by DADS could explain the inhibition of EMT, invasion and proliferation in gastric cancer cells.

[Identification of Sulfate Sources in the Groundwater System of Zaozhuang: Evidences from Isotopic and Hydrochemical Characteristics].

Karst groundwater is an important source of water supply for the industrial and agricultural proposes and drinking water in Zaozhuang City. In recent years, with the development of industrialization and increasing of domestic water consumption, the sulfate pollution of karst groundwater has become a serious problem. 36 samples of surface and different depth of groundwater were collected in southern Zaozhuang City in August, 2014. Based on the analysis of the hydrochemical composition and the isotopic characteristics of δD, δ18O-H2O, and δ34 S-SO42-, this paper analyzed the influence of hydrogeochemical evolution of groundwater and human input in the area, in order to identify the scope and ways of sulfate pollution. The results showed that the basic hydrochemical type was HCO3·SO4-Ca, formation of geochemical components mainly included the dissolution of carbonate and sulfate minerals, oxidation of pyrite and the influence of human activities. Moreover, the main recharge of groundwater in study area was the atmospheric precipitation. The hydraulic connection was closely linked between the surface water and different depth of groundwater. The variation range of groundwater δ34 S-SO42- values was from 0.2‰ to 9.3‰, and the relationship between the δ34 S-SO42- value and SO42- value of groundwater showed different sources of sulfate. The sources of sulfate in groundwater included the dissolution of gypsum, the oxidation of pyrite, the leaching of fertilizer and infiltration of domestic sewage and industrial wastewater. In addition to the original geological factors, wastewater infiltration of industrial and mining enterprises was the main reason for the increase of sulfate content in the groundwater.

Relationship between SERPING1 rs2511989 polymorphism and age-related macular degeneration risk: a meta-analysis.

PURPOSE: We conducted a meta-analysis aiming to evaluate the relationship between a common polymorphism (rs2511989 G>A) in the SERPING1 gene and the risk of age-related macular degeneration (AMD). METHODS: The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before November 1, 2013, without any language restrictions. A meta-analysis was conducted using STATA 12.0 software. We calculated a crude odds ratio (OR) with a 95% confidence interval (95% CI) to evaluate the relationships under five genetic models. RESULTS: Seven case-control studies with a total of 7,159 patients with AMD and 5,797 healthy subjects met the inclusion criteria. The results of our meta-analysis showed that the SERPING1 rs2511989 polymorphism might be correlated with an increased risk of AMD (G allele versus A allele: OR = 1.09, 95% CI = 1.03-1.15, p = 0.020; GG + GA versus AA: OR = 1.14, 95% CI = 1.03-1.26, p = 0.014; GG versus GA+AA: OR = 1.10, 95% CI = 1.02-1.19, p = 0.012; GG versus AA: OR = 1.20, 95% CI = 1.07-1.34, p = 0.002; respectively). Results of subgroup analysis by ethnicity revealed positive correlations between the SERPING1 rs2511989 polymorphism and risk of AMD among Caucasians under five genetic models (all p<0.05), but not among Asians (all p>0.05). CONCLUSIONS: The current meta-analysis shows that the SERPING1 rs2511989 polymorphism may have a positive effect on the risk of AMD, especially among Caucasians.

[Analysis of optic crosstalk correction for pushbroom hyperspectral data].

Based on the imaging process of pushbroom hyperspectral imager, a correction method for optic crosstalk was developed. An area that has white calibration target was selected as reference data. The target pixels crosstalk quantity was gained using the subtraction between the two lines of reference data, and it was fitted to restrain noise. Using recursion method, crosstalk quantity of single pixel was calculated from the fitted function, and it could be used to correct the optical crosstalk of the whole data. Three PHI (pushbroom hyperspectral imager) data which have different ground scene were corrected. It was showed that optical crosstalk in corrected data is lightened obviously, and the data quality is improved effectively in both the spectral dimension and spatial dimension. The spectral changing caused by optical crosstalk is also corrected, and the bands with definition increased more than 50% accounts for 83% of the total bands. Optic crosstalk is obtained form hyperspectral data itself which is independent of other data source. It is proved that the correction method is valid, and it is applicable for different ground type. The correction method also provides a way to measure the optic crosstalk of hyperspectral imager in the lab.

Chiral separation of ß-blockers by MEEKC using neutral microemulsion: Analysis of separation mechanism and further elucidation of resolution equation.

Based on the investigation of the effect of microemulsion charge on the chiral separation, a new chiral separation method with MEEKC employing neutral microemulsion was established. The method used a microemulsion containing 3.0% (w/v) neutral surfactant Tween 20 and 0.8% (w/v, 30 mM) dibutyl l-tartrate in 40 mM sodium tetraborate buffer to separate the enantiomers of ß-blockers. The effect of major parameters on the chiral separation was investigated. The applied voltage had little effect on the resolution, but the chiral separation could be improved by suppressing the EOF. Nine racemic ß-blockers obtained relatively good enantioseparation after appropriate concentrations of tetradecyl trimethyl ammonium bromide were added into the microemulsion to suppress the EOF. These results were explained based on the analysis of the separation mechanism of the method and deduced separation equations. The resolution equation of the method was further elucidated. It was found that the fourth term in the resolution equation, an additional term compared to the conventional resolution equation for column chromatography, represents the ratio of the relative movement distance between the analyte and microemulsion droplets relative to the effective capillary length. It can be regarded as a correction for the effective capillary length. These findings are significant for the development of the theory of MEEKC and the development of new chiral MEEKC method.

Protection of ultra-filtration extract from Danggui Buxue Decoction on oxidative damage in cardiomyocytes of neonatal rats and its mechanism.

OBJECTIVE: To investigate whether the administration of the ultra-filtration extract from Danggui Buxue Decoction (EDBD) was able to protect cardiomyocytes from oxidative injury of rats induced by hydrogen peroxide (H(2)O(2)) and its potential mechanism. METHODS: Myocardial cells from 1- to 2-day-old neonatal rats were cultured in Dulbecco's modified Eagle's medium low-glucose and Ham's F12 medium (1:1), and the cellular injury was induced by H(2)O(2). The ultra-filtration extract mixture from Angelica sinensis and Hedysarum polybotrys was given in three doses of 3.75, 7.5, and 15 mg/mL. Morphological changes of cardiomyocytes were observed by microscope. Survival rate of myocardial cells was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cardiomyocyte damages were estimated by detecting lactate dehydrogenase (LDH) and creatine kinase (CK) releases in the medium, superoxide dismutase (SOD) activities, and intracellular malondialdehyde (MDA) and myeloperoxidase (MPO) contents. The levels of caspase-3 and heat shock protein 70 (hsp70) mRNA expression in cardiomyocytes were measured by reverse transcription polymerase chain reaction. RESULTS: The EDBD could protect the cardiomyocytes from H(2)O(2) injury in a dosedependent manner (3.75, 7.50, and 15.00 mg/mL). The EDBD could significantly decrease LDH and CK leakages and intracellular MDA and MPO contents, increase SOD activity, up-regulate hsp70 expression, and down-regulate caspase-3 expression. CONCLUSION: The EDBD has protection on cardiomyocytes injured by H(2)O(2) through improving cell antioxidant ability, up-regulating hsp70 expression, and inhibiting caspase-3 activity.

Micelle to solvent stacking of two alkaloids in nonaqueous capillary electrophoresis.

This paper for the first time describes the development of micelle to solvent stacking (MSS) to nonaqueous capillary electrophoresis (NACE). In this proposed MSS-NACE, sodium dodecyl sulfate (SDS) micelles transport, release, and focus analytes from the sample solution to the running buffer using methanol as their solvent. After the focusing step, the focused analytes were separated via NACE. The focusing mechanism and influencing factors were discussed using berberine (BBR) and jatrorrhizine (JTZ) as model compounds. And the optimum condition was obtained as following: 50 mM ammonium acetate, 6% (v/v) acetic acid and 10 mM SDS in redistilled water as sample matrix, 50 mM ammonium acetate and 6% (v/v) acetic acid in pure methanol as the running buffer, -20 kV focusing voltage with 30 min focusing time. Under these conditions, this method afforded limits of detection (S/N=3) of 0.002 µg/mL and 0.003 µg/mL for BBR and JTZ, respectively. In contrast to conventional NACE, the concentration sensitivity was improved 128-153-fold.

A novel cross-H-channel interface for flow injection-capillary electrophoresis to reduce sample requirement and improve sensitivity.

In this study, a cross-H-channel interface was constructed for coupling flow injection with capillary electrophoresis (FI-CE) to reduce sample requirement and sensitivity loss in the typical FI-CE. Based on this cross-H-channel interface, a new FI-CE system was established, in which sample introduction was performed by directly injecting sample solution along a thin capillary (50 µm, i.d.) to the interface from an injection syringe. The sample requirement was reduced distinctly and usual sample dilution in the sample transport process was obviously decreased, thereby spontaneously enhancing the sensitivity. Moreover, because of the unique construction of the cross-H-channel interface, field amplified sample stacking (FASS) and high-speed CE were skillfully combined to further improve the sensitivity and to shorten separation time. The versatility of this new FI-CE was demonstrated by determination of ephedrine (E) and pseudoephedrine (PE) in human urine. Up to 45 repeated injections per hour and clearly baseline separation of E and PE in less than 1 min were achieved, giving limits of detection (LODs) of 0.23 and 0.21 µg mL(-1) for E and PE, respectively, and yielding relative standard deviation (RSD) values of the migration time and the peak height (n=5) of 2.6% and 3.1% for E, 2.3% and 3.3% for PE, respectively. In contrast to typical FI-CE, approximately 8-250-fold decreases in sample volume requirement, 7-fold shortening in separation time and 50-fold improvements in sensitivity were obtained.

Diallyl disulfide induces apoptosis in human leukemia HL-60 cells through activation of JNK mediated by reactive oxygen.

Diallyl disulfide (DADS) is a chemopreventive agent that can induce apoptosis in many tumor cells. Reactive oxygen species (ROS) are important mediators in apoptosis induced by various stimuli, including chemopreventive agents. The phosphotransferase c-JUN N-terminal kinase (JNK) has been shown to regulate apoptosis. In this study, we found that DADS-induced apoptosis in human leukemia HL-60 cells is mediated by ROS-activated JNK. The DADS-treated HL-60 cells showed a dose- and time-dependent decrease in cell viability and proliferation. Agarose gel electrophoresis of cells treated with 10.0 or 20.0 mg/L DADS for 24 h showed a characteristic ladder pattern in their DNA. Levels of DADS-induced ROS, as measured by 2',7'-dichlorofluorescein diacetate (DCFH-DA) fluorescence, also showed dose- and time-dependent increases in HL-60 cells. Activity of JNK was induced by DADS in a dose-dependent manner; HL-60 cells exposed to 10.0 mg/L DADS for 8 h showed maximum levels of phosphorylated JNK, which decreased when exposed for additional 4h. In contrast, Sp600125, a specific inhibitor of JNK, blocked apoptosis of HL-60 cells exposed to DADS. N-Acetylcysteine (NAC), a known antioxidant, also decreased ROS generation, effectively blocked apoptosis, and decreased DADS-induced phosphorylated JNK levels. These results suggest that JNK is involved in DADS-induced ROS-mediated apoptosis in HL-60 cells.