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Background Arsenic (As3+) is a carcinogen with considerable environmental and occupational relevancy. Its mechanism of action and methods of prevention remain to be investigated. Previous studies have demonstrated that ROS is responsible for As3+-induced cell transformation, which is considered as the first stage of As3+ carcinogenesis. The NF-E2 p45-related factor-2 (Nrf2) signaling pathway regulates the cellular antioxidant response, and activation of Nrf2 has recently been shown to limit oxidative damage following exposure to As3+ Methods and results In this study, molecular docking was used to virtually screen natural antioxidant chemical databases and identify molecules that interact with the ligand-binding site of Keap1 (PDB code 4L7B). The cell-based assays and molecular docking findings revealed that curcumin has the best inhibitory activity against Keap1-4L7B. Co-immunoprecipitation (Co-IP) results indicated that curcumin is a potent Keap1 Kelch domain-dependent Nrf2 activator that stabilizes Nrf2 by hindering its ubiquitination. The increased activation of Nrf2 and its target antioxidant genes by curcumin could significantly decrease As3+-generated ROS. Moreover, curcumin induced autophagy in As3+-treated BEAS-2B via inducing autophagy by the formation of a p62/LC-3 complex and increasing autophagic flux by promoting transcription factor EB (TFEB) and lysosome-associated membrane protein 1 (LAMP1) expression. Knockdown of Nrf2 abolished curcumin-induced autophagy and downregulated ROS. Further studies showed that inhibition of autophagosome and lysosome fusion with bafilomycin a1 (BafA1) could block curcumin and prevented As3+-induced cell transformation. These results demonstrated that curcumin prevents As3+-induced cell transformation by inducing autophagy via the activation of the Nrf2 signaling pathway in BEAS-2B cells. However, overexpression of Keap-1 showed a constitutively high level of Nrf2 in As3+-transformed BEAS-2B cells (AsT) is Keap1-independent regulation. Overexpression of Nrf2 in AsT demonstrated that curcumin increased ROS levels and induced cell apoptosis via the downregulation of Nrf2. Further studies showed that curcumin decreased the Nrf2 level in AsT by activating GSK-3β to inhibit the activation of PI3K/AKT. Co-IP assay results showed that curcumin promoted the interaction of Nrf2 with the GSK-3β/β-TrCP axis and ubiquitin. Moreover, the inhibition of GSK-3β reversed Nrf2 expression in curcumin-treated AsT, indicating that the decrease in Nrf2 is due to activation of the GSK-3β/β-TrCP ubiquitination pathway. Furthermore, in vitro and in vivo results showed that curcumin induced cell apoptosis, and had anti-angiogenesis and anti-tumorigenesis effects as a result of activating the GSK-3β/β-TrCP ubiquitination pathway and subsequent decrease in Nrf2. Conclusions Taken together, in the first stage, curcumin activated Nrf2, decreased ROS, and induced autophagy in normal cells to prevent As3+-induced cell transformation. In the second stage, curcumin promoted ROS and apoptosis and inhibited angiogenesis via inhibition of constitutive expression of Nrf2 in AsT to prevent tumorigenesis. Our results suggest that antioxidant natural compounds such as curcumin can be evaluated as potential candidates for complementary therapies in the treatment of As3+-induced carcinogenesis.

Objective: We aimed to compare amyloid deposition at the lobar cerebral microbleed (CMB) sites of cerebral amyloid angiopathy (CAA), Alzheimer’s disease (AD), and cognitively normal healthy controls (NC) and to propose a novel diagnostic method for differentiating CAA patients from AD patients with integrated 11C-Pittsburgh compound B (PIB) positron emission tomography (PET)/magnetic resonance (MR) and assess its diagnostic value.Methods: Nine CAA, 15 AD patients, and 15 NC subjects were enrolled in this study. Each subject underwent an 11C-PIB brain PET/MR examination. Susceptibility weighted imaging was assessed to detect CMB locations, and standardized uptake value ratios (SUVRs) were measured at these sites. Cortical PIB distributions were quantitatively evaluated. Patients with CAA, AD, and NC subjects were compared with global and regional cortical SUVRs at CMB cites. The diagnostic accuracy of MRI, PIB-PET, and PET/MR in differentiating CAA and AD was evaluated.Results: Lobar CMBs were detected in all the CAA patients, eight of the 15 AD patients (53.3%), and four of the 15 NC subjects (26.7%), respectively. The PIB deposition at CMB sites was significantly higher in CAA patients compared with AD patients and NC subjects in terms of SUVR (1.72 ± 0.10 vs. 1.42 ± 0.16 and 1.17 ± 0.08; p < 0.0001). The PIB deposition was associated with CMB locations and was greatest in the occipital and temporal regions of CAA patients. The global cortical PIB deposition was significantly higher in CAA than in NC subjects (1.66 ± 0.06 vs. 1.21 ± 0.06; p < 0.0001) and significantly lower than in AD patients (1.66 ± 0.06 vs. 1.86 ± 0.17; p < 0.0001). In contrast, the occipital/global PIB uptake ratio was significantly increased in CAA (occipital/global ratio, 1.05 ± 0.02) relative to AD patients (1.05 ± 0.02 vs. 0.99 ± 0.04; p < 0.001). PET/MR had a higher accuracy (sensitivity, 88.9%; specificity, 93.3%) than separate PET and MR.Conclusion: Our results indicate that the CMBs occur preferentially at loci with concentrated amyloid. By combining lobar CMBs with regional cortical amyloid deposition, the proposed workflow can further improve CAA diagnostic accuracy compared to each method alone. These findings improve our knowledge regarding the pathogenesis of CMBs and highlight the potential utility of PIB-PET/MR as a non-invasive tool for distinguishing CAA and AD patients.

Chinese herbal medicines (CHMs) are widely used in Asian countries. They show multiple pharmacological activities, including antiviral activities. The 5′-long terminal repeat (LTR) region of HIV-1, required for viral transcription, is a potential drug target for HIV-1 reactivation and intrinsic cell death induction of infected or latently infected cells. Modulation of HIV-1 reactivation requires interactions between host cell proteins and viral 5′-LTR elements. By evaluation of two CHMs- Xanthium strumarium and Pueraria montana, we found that 1) X. strumarium reactivated HIV-1 latently infected cells in J-Lat 8.4, J-Lat 9.2, U1, and ACH-2 cells in vitro; 2) 27 nuclear regulatory proteins were associated with HIV-1 5′-LTR using deoxyribonucleic acid affinity pull-down and LC-MS/MS analyses; and 3) among them, silencing of XRCC6 reactivated HIV-1 5′-LTR transcriptional activity. We found that X. strumarium inhibits the 5′-LTR associated XRCC6 nuclear regulatory proteins, increases its viral 5′-LTR promoter transcriptional activity, and reactivates HIV-1 latently infected cells in vitro. These findings may contribute to understanding the 5′-LTR activity and the host cell nuclear regulatory protein machinery for reactivating HIV-1 and for future investigations to eradicate and cure HIV-1 infection.

Herein, 10-fold electrochemiluminescence (ECL) enhancement from a porous SnO2 nanocrystal (SnO2 NC) xerogel (vs discrete SnO2 NCs) was first observed with NO3- as a novel coreactant. This new booster phenomenon caused by pore characteristic was defined as "pore confinement-induced ECL enhancement", which originated from two possible reasons: First, the SnO2 NC xerogel with hierarchically porous structure could not only localize massive luminophore near the electrode surface, more importantly, but could accelerate the electrochemical and chemiluminescence reaction efficiency because the pore channels of xerogel could promote the mass transport and electron transfer in the confined spaces. Second, the NO3- could be in situ reduced easily to the active nitrogen species by means of the pore confinement effect, which could be served as a new coreactant for nanocrystal-based ECL amplification with the excellent stability and good biocompatibility. As a proof of concept, a facile and sensitive sensing platform for SO32- detection has been successfully constructed upon effectively quenching of SO32- toward the SnO2 NC xerogel/NO3- ECL system. The key feature about this work presented a grand avenue to achieve the strong ECL signal, especially from weak emitters, which gave a fresh impetus to the construction of new-generation of surface-confined ECL platform with potential applications in ECL imaging and sensing.

Phase equilibrium data for binary system of (CO2 + styrene, CO2 + 1,4-dioxane, and CO2 + N,N-dimethylformamide) were measured at temperatures from 308.2 K to 353.2 K and at pressures up to 12 MPa by means of a variable-volume view cell phase equilibrium analyser (PEA). The isothermal phase boundary data include measured phase transition of bubble, dew, and near critical pressures. The experimental results were correlated by means of the Peng-Robinson equation of state in conjunction with the van der Waals one-fluid mixing rules. The new data obtained in this work serve to clarify the inconsistencies among the literature values.

The heterogeneous kinetics and adsorption behavior for the esterification of acrylic acid and ethanol were studied by using a fixed-bed reactor over an acidic cation-exchange resin beads, Amberlyst 35. The reaction experiments were conducted at 318.15 K–348.15 K under atmospheric pressure. The influences of molar ratios of ethanol to acrylic acid in the feed (θBo) and the mass transfer resistances on the kinetic behavior were also investigated. The experimental results show that the equilibrium conversion of acrylic acid increases with increasing reaction temperature and θBo. Moreover, the adsorption experiments were also made to determine the relative adsorption strengths among the reacting species. The results reveal that the magnitude of adsorption strengths obeyed the sequence of water > acrylic acid > ethanol > ethyl acrylate. The kinetic data obtained from the present study were correlated with the ideal-quasi-homogeneous (IQH), the non-ideal-quasi-homogeneous (NIQH), the Langmuir-Hinshelwood-Hougen-Waston (LHHW), the Eley-Rideal (ER) models, the modified LHHW (M-LHHW) and the modified ER (M-ER). The best-fitted values of the kinetic parameters were reported. The correlated results indicated that the M-LHHW model provides the best representation for this reaction system.

Densities are measured for two binary systems of oligomeric blends, polyethylene glycol mono-4-octylphenyl ether) (PEGOPE) + polyethylene glycol mono-laurate (PEGML) and polyethylene glycol mono-4-nonylphenyl ether (PEGNPE) + PEGML, at temperatures from 298.15 K to 348.15 K and pressures up to 50 MPa. The excess volumes are negative for these two binary systems over the majority of composition range, except for the regions near pure components, in which the values may change into positive. Tait equation represents accurately for the pressure-effect on the liquid densities. Additionally, a generalized equation with two characteristic parameters correlates well the P-V-T data over the entire experimental conditions for each binary system. Those P-V-T data are also correlated satisfactorily with the Flory-Orwoll-Vrij (FOV) and the Schotte equations of state with one binary interaction parameter for each oligomeric blend system.

This study conducts a correlation exploration of CYP2C19 gene polymorphism and clopidogrel resistance in Han Chinese patients with cerebral infarction in Guizhou Region. A total of 270 Han Chinese patients with cerebral infarction, who were hospitalized in our hospital from January 2016 to January 2018, are selected. These patients were divided into 2 groups, clopidogrel resistance group (n = 60) and clopidogrel sensitive group (n = 210). According to the TEG results, the CYP2C19 gene polymorphism detection was carried out by using the PCR-RFLP method, while IL-6 level in the patient's blood was measured by using the ELISA method. The resistance group occupies 22.22%. The platelet inhibition ratio of the resistance group was 23 ± 7%, which was significantly lower than that of the sensitive group (65 ± 13%), and the difference was statistically significant (P

Age-related macular degeneration (AMD) is a major cause of visual impairment and blindness among the elderly. AMD is characterized by retinal pigment epithelial (RPE) cell dysfunction. However, the pathogenesis of AMD is still unclear, and there is currently no effective treatment. Accumulated evidence indicates that oxidative stress and autophagy play a crucial role in the development of AMD. H2S is an antioxidant that can directly remove intracellular superoxide anions and hydrogen peroxide. The purpose of this study is to investigate the antioxidative effect of H2S in RPE cells and its role in autophagy. The results show that exogenous H2S (NaHS) pretreatment effectively reduces H2O2-induced oxidative stress, oxidative damage, apoptosis, and inflammation in ARPE-19 cells. NaHS pretreatment also decreased autophagy levels raised by H2O2, increased cell viability, and ameliorated cell morphological damage. Interestingly, the suppression of autophagy by its inhibitor 3-MA showed an increase of cell viability, amelioration of morphology, and a decrease of apoptosis. In summary, oxidative stress causes ARPE-19 cell injury by inducing cell autophagy. However exogenous H2S is shown to attenuate ARPE-19 cell injury, decrease apoptosis, and reduce the occurrence of autophagy-mediated by oxidative stress. These findings suggest that autophagy might play a crucial role in the development of AMD, and exogenous H2S has a potential value in the treatment of AMD.

Hydroxyapatite scaffolds (HASs) are widely studied as suitable materials for bone replacement scaffolds due to their chemical similarities to organic materials. In our previous study, a novel HAS with a 25–30-µm groove structure (HAS-G) exhibited enhanced osteogenesis of bone mesenchymal stromal cells (BMSCs) compared with HAS, potentially by modulating the macrophage-induced immune microenvironment. However, the exact effects of different surface patterns on the physiological processes of attached cells is not known. The present study aimed to determine the effects of HAS-G on the osteogenesis and physiological processes in BMSCs. Cell counting kit-8 assays and propidium iodide staining followed by flow cytometry were performed, and the results demonstrated that both in normal medium and differentiating medium, HAS-G promoted cell proliferation by decreasing the proportion of G1/G0 cells and decreased reactive oxygen species (ROS) accumulation in BMSCs compared with HAS. Detection markers of osteogenesis revealed that compared with HAS, HAS-G increased runt-related transcription factor 2, osteocalcin and osteopontin protein levels and promoted osteogenesis, which was further confirmed by Alizarin Red S staining. Following JC-1 staining, it was observed that HAS-G maintained the mitochondrial membrane potential, similar to that achieved by N-acetylcysteine pretreatment. In addition, compared with those of HAS, HAS-G decreased mitochondrial ROS levels, which potentially contributed to the promotion of osteogenesis. The results also demonstrated that HAS-G inhibited mitophagy induced by ROS accumulation and ATP synthesis compared with HAS. In conclusion, HAS-G decreased ROS accumulation and mitophagy and thus promoted osteogenesis of BMSCs, indicating that ROS modulation of HAS-G may serve a key role in osteogenesis.

Nonadiabatic photodissociation dynamics of thiophenol (PhSH) and deuterated thiophenol (PhSD) via the 1ππ* state was investigated by a reduced three-dimensional (3D) quantum model based on the associated 3D diabatic potential energy surfaces constructed at the explicitly correlated multireference configuration interaction (MRCI-F12) level with the cc-pVTZ-F12 basis. The lifetimes of the low-lying vibronic S1 states for PhSH and PhSD were calculated using a low-storage filter diagonalization method and were in reasonably good agreement with the available experimental results. The nonadiabatic effect was further examined in the photodissociation process by comparing the results in diabatic and adiabatic models. It was found that the adiabatic lifetimes were about 2–4 times shorter than the exact ones in the diabatic model for both PhSH and PhSD. More importantly, the exact ground wave function including the geometric phase (GP) possessed a node along the C–C–S–H/C–C–S–D torsional coordinate, while the node ...

Pathogens are able to exploit specific glycosaminoglycans (GAGs), especially iduronic acid (IdoA)-containing GAGs, to invade the host. By analyzing Escherichia coli proteome chip data, we identified the interactomes of three IdoA-containing GAGs: heparin, heparin sulfate (HS), and chondroitin sulfate B (CSB). Using non-IdoA-containing GAG, chondroitin sulfate C, as a negative control, 157 proteins specifically binding with IdoA-containing GAGs were revealed in the present study. These proteins showed functional enrichment in protein synthesis and metabolism. Fifteen proteins which commonly interacts with three IdoA-containing GAGs were further examined. The regular expression for motif showed these common IdoA interactome shared a conserved sequence. Among them, we identified a second flagellar system outer membrane protein, MbhA. The MbhA has Kd values of 8.9 × 10−8 M, 5.3 × 10−7 M, and 1.79 × 10−7 M to interact with heparin, HS, and CSB, respectively. Using flow cytometry, we confirmed that the MbhA protein can bind to human epithelial cells HCT-8. Overexpression of mbhA increased the percentage of invasion in E. coli which lacks a second flagellar system. Moreover, pre-blocking of HCT-8 cells with MbhA inhibited the bacterial invasion, implying the importance of the direct interaction of MbhA and the host cell surface on bacterial invasion. Significance We analyzed the Escherichia coli proteomic data to elucidate the interactomes of three different IdoA-containing GAGs (heparin, HS, and CSB) because these IdoA-containing GAGs can mediate bacterial invasion to the host. Through proteomic and systematic analysis, a second flagellar system outer membrane protein, MbhA, was also identified in the present study. Affinity assay confirmed that MbhA can bind to three IdoA-containing GAGs heparin, HS, and CSB. The result of flow cytometry also showed MbhA can interact with human epithelial cells HCT-8. Results of bacteria invasion assay showed overexpression of mbhA promoted the bacterial invasion. Moreover, pre-blocking of HCT-8 cells with MbhA also reduced the percentage of bacterial invasion. These findings correspond well that MbhA is one of invasion factors.

A visual and volume-variable high-pressure phase equilibrium analyzer was used for measuring the isothermal vapor-liquid equilibrium (or vapor-liquid-liquid) phase boundaries of CO2 with the mixed solvents of ethanol/water = 9/1, dimethyl sulfoxide (DMSO)/water = 9/1, and N,N-dimethyl formamide (DMF)/water = 7.5/2.5 in molar ratio at temperatures from 298.2 K to 348.2 K over wide composition range, including near critical regions. The isothermal phase equilibrium data obtained from this work are compared with those of water-free binary systems to investigate the effect of phase boundary shifts caused by introducing the phase modifier, water, into the organic solvents. The comparison shows that the bubble, dew, and critical pressures substantially increase in the presence of water for each system, especially for DMSO-containing system. The Peng-Robinson equation of state with Mathias-Copemen alpha function and the Wong-Sandler mixing rule is employed to the phase equilibrium calculation. While the UNIFAC model estimates the excess Helmholtz free energy at infinite pressure, the binary interaction parameters for calculating the second virial coefficient are determined by the phase equilibrium data of constituent binaries. The obtained parameters are directly adopted to the phase boundary predictions for the investigated ternary systems.

Metal-free oxidative coupling of amines is achieved simply by heating their dimethyl sulfoxide (DMSO) solution under oxygen as oxidant without any other catalysts or additives, accompanied by the formation of an equimolar amount of dimethyl sulfone (DMSO2). EPR experiments indicate that the reaction proceeds via a radical pathway. DMSO may play a triple role as solvent, radical initiator and co-reductant.

The liquid-liquid equilibrium (LLE) properties were measured for the ternary systems of water + acrylic acid + ethyl acrylate, water + ethanol + ethyl acrylate, water + acrylic acid + n-butyl acrylate, and water + n-butanol + n-butyl acrylate at temperatures ranging from 283.15 K to 318.15 K under 101.3 kPa. The ternary system of water + n-butanol + n-butyl acrylate behaves as type-II LLE and the other three systems are categorized as type-I LLE. The new LLE tie-lines data were correlated with the NRTL and UNIQUAC models. The UNIQUAC model yields slightly better results than the NRTL model, except for the system of water + acrylic acid + ethyl acrylate. Satisfactory results can also obtained from the UNIQUAC model by using the parameters determined from the constituent binary phase equilibrium data for the type-II system (water + n-butanol + n-butyl acrylate), but substantial deviations were found as the UNIQUAC model using the parameters estimated from the group-contribution based UNIFAC model.

Objective Apatinib, a small molecule inhibitor of VEGFR-2 tyrosine kinase, shows strong anti-tumour activity against various tumours. The function of apatinib in ovarian cancer, however, remains unclear. This study was conducted to investigate the effects and potential mechanisms by which apatinib modulates the biological function of ovarian cancer cells in vitro and in vivo. Methods The effects of apatinib on ovarian cancer cells were determined by assessing cell viability, migration and invasion. The cell cycle distribution and apoptosis of ovarian cancer cells were analysed using flow cytometry. Western blotting was performed to determine the levels of signalling pathway markers. A mouse xenograft model was used to evaluate the efficacy of apatinib in preventing tumour growth. Results Apatinib did not appreciably affect ovarian cancer cell proliferation and vitality, but did inhibit ovarian cancer cell migration. Apatinib suppressed the epithelial-mesenchymal transition in ovarian cancer cells by inhibiting the JAK/STAT3, PI3K/AKT and Notch signalling pathways. Apatinib effectively inhibited tumour growth in vivo. Conclusion Based on our findings, apatinib is a highly potent, orally active anti-angiogenic and anti-ovarian cancer agent.

Temporal changes in the concentrations of dioxin-like (DL) polychlorinated biphenyls (PCBs) in environmental and biological matrices in China are not well understood. We determined the DL-PCB concentrations in pooled serum samples from the general population of Weifang City, Shandong Province, China in 2011 (n = 305) and 2017 (n = 495). The total DL-PCB concentration was 3.48 ± 1.31 ng/g lipid (mean ± standard deviation) in 2011 and 2.82 ± 1.73 ng/g lipid (19% lower) in 2017, but the difference was not statistically significant (p = 0.347). The DL-PCB concentrations and toxic equivalent concentrations were much lower in the serum from Weifang residents than have been found in serum from the inhabitants of other parts of the world. The concentrations of most of the DL-PCB congeners followed different downward temporal trends, but the PCB-118 concentration was higher in 2017 than in 2011. The temporal changes in the PCB concentrations and compositions in the samples from the general population of Weifang indicated that there may a new source of unintentionally produced PCBs in Weifang.

Accumulating evidence indicates that overconsumption of ethanol contributes in many ways to the pathogenesis of hepatic injury. Although studies indicate that taurine decreases lipogenesis, oxidative stress, and inflammatory cytokines, the protective effect of taurine against alcohol-induced liver injury is still unclear. To clarify the precise signaling involved in the beneficial effect of taurine on alcohol-induced liver injury, rats were randomly divided into four treatment groups: (1) control (Ctl), (2) alcohol (Alc), (3) Alc+taurine (Tau), and (4) Alc+silymarin (Sil). The Tau and Sil groups had lower lymphocyte infiltration and significantly lower TLR-4/MyD88 and IκB/NFκB compared to the Alc group. The inducible nitric oxide synthase (iNOS), C-reactive protein (CRP), tumor necrosis factors (TNF)-α, interleukin (IL)-6, and IL-1β were also significantly lower in the Tau and Sil groups than in the Alc group. The experimental results indicated that hepatoprotection against alcohol-induced inflammation may be mediated by decreased TLR-4/MyD88 signaling.

New reduced three-dimensional (3D) diabatic potential energy surfaces (PESs) involving the 1ππ, 1ππ*, and 1πσ* states for the nonadiabatic photodissociation C6H5SH(S0) + hv → C6H5SH(1ππ*/1πσ*) → H + C6H5S•(A/X) were constructed at a high computational level, namely explicitly correlated multireference configuration interaction (MRCI-F12) method with the cc-pVTZ-F12 basis. The diabatization of the PESs was achieved by a simple, efficient, and reliable “regularized diabatization” method [Koppel, H.; Gronki, J.; Mahapatra, S. J. Chem. Phys. 2001, 115, 2377–2388]. The dissociation energy of the S0 state and the excitation energies of the excited S1 and S2 states were found to be in reasonably good agreement with the experimental values. The vibronic energy levels of the thiophenol (PhSH) and deuterated thiophenol (PhSD) for S0 and S1 states were calculated using a three-dimensional model, and they are in reasonably good agreement with the available experimental results, which validate the high accuracy of the...

Ethanol was used as a cosolvent to enhance the solubility of disperse dyestuffs in supercritical fluids. In the presence of ethanol, from (1 to 5) mol%, the gas–solid equilibrium data of the Disperse Red 82 and modified Disperse Yellow 119 in supercritical carbon dioxide or nitrous oxide have been measured at temperatures from (353.2 to 393.2) K and pressures from (15.0 to 30.0) MPa. The experimental results show that the solubility increases substantially, up to (9 to 25)-fold, by adding 5 mol% of ethanol to the supercritical fluids. In the presence of cosolvent ethanol, the solubility enhancements in nitrous oxide system are much greater than that in carbon dioxide system for modified Disperse Yellow 119 at the same temperature and pressure. The solubility data were correlated with the Chrastil and the Mendez-Santiago and Teja models. The Mendez-Santiago and Teja model yields slightly better results than Chrastil model.

The solubility data of two fluorinated and non-steroidal anti-inflammatory drugs, niflumic acid (CAS No. 4394-00-7) and celecoxib (CAS No. 169590-42-5), in supercritical carbon dioxide were measured with a semi-flow type phase equilibrium apparatus at temperatures ranging from 313.2 K to 353.2 K and pressures up to 31 MPa. At the highest extraction temperature and pressure, the solubilities are 2.09 × 10 −5 and 1.52 × 10 −5 in mole fraction for niflumic acid and celecoxib, respectively. The saturated solubility data were correlated with the Chrastil model, the Mendez-Santiago–Teja equation, and the Peng–Robinson equation of state. The Chrastil model fitted the experimental data to about within the experimental uncertainty. The correlated results of the Mendez-Santiago–Teja model confirmed the consistency of the solubility data over the entire experimental conditions. Incorporating with two-parameter van der Waals one-fluid mixing rules, the Peng–Robinson equation of state represents satisfactorily the gas–solid equilibrium behavior of niflumic acid and celecoxib in supercritical carbon dioxide.

BackgroundThe purpose of this study was to investigate the association between the use of herbal medicine containing aristolochic acid (AA) and the risk of cancers among patients with diabetes.MethodsWe conducted a population-based cohort study on patients older than 18 years who had a diagnosis of diabetes (ICD-9 codes 250) between January 1, 1997 and December 31, 2010. To ensure comparability, we included only patients with diabetes who had visited traditional Chinese medicine clinics between January 1, 1997 and one year before the diagnosis of cancer or the censor dates. The use of herbal medicine containing AA was identified from January 1, 1997 to October 31, 2003 (the ban of herbs containing AA in November 2003). Each patient was individually tracked to identify incident cases of cancer (140–208) between January 1, 1999 and December 31, 2013.FindingsA total of 4 30 377 male and 4 31 956 female patients with diabetes were identified by using the National Health Insurance Research Database in Taiwan. There were 37 554 and 31 535 cancers during the follow-up period. AA use increased the risks of incident liver (155.0), kidney (189.0), pelvis and ureter (189.1, 189.2), and bladder (188) cancer in male patients with diabetes in a dose-dependent relationship. Similarly, there were increased risks of incident liver, pelvis and ureter, and bladder cancer in female diabetic patients in a dose-dependent manner.InterpretationOur study suggests that AA exposure plays an important role in the carcinogenesis of liver, kidney, pelvis, ureter, and bladder cancers in patients with diabetes.

A visual and volume-variable high-pressure phase equilibrium analyzer was used for measuring the vapor–liquid phase boundaries of the ternary systems containing carbon dioxide and mixed solvents of dimethyl sulfoxide (DMSO) + ethanol or chloroform + methanol at temperatures from 298.15 K to 348.15 K over wide composition ranges including near critical points. Four pseudo-binary systems of carbon dioxide plus mixed solvents with constant molar ratios of DMSO/ethanol = 3/7, 5/5, 7/3, and chloroform/methanol = 1/2, were studied in this work. The critical conditions at each investigated temperature were estimated from the experimental isothermal phase boundaries by interpolation. The Peng–Robinson equation of state with the two-parameter van der Waals mixing rules was applied to calculate the phase boundaries. The experimental values were compared with the predicted results from the Peng–Robinson equation using the binary interaction parameters determined from the vapor–liquid equilibrium data of the constituent binaries. The agreement is reasonably well for carbon dioxide + chloroform + methanol, but obvious overestimations are found near the critical regions of carbon dioxide + DMSO + ethanol, especially at higher temperatures.

We recently demonstrated the chemical composition of Hibiscus sabdariffa polyphenol extracts (HPE), and its anti-insulin resistance property using a type 2 diabetic rat model. In the present study, we examined whether HPE prevents diabetic nephropathy, and its putative regulations of the pathogenic markers. HPE significantly inhibited albuminuria and the elevation of clearance of creatinine (CCr) caused by early diabetic nephropathy. Histological findings revealed that HPE inhibited fat deposition and advanced glycation end-products (AGE) expression in kidneys of type 2 diabetic rats. The increase of tubular connective tissue growth factors (CTGFs) and glomerular cluster of differentiation 31 (CD31) were also ameliorated by HPE. HPE reversed collagen accumulation, decreased angiotensin II type 1 receptor (AT-1) elevation, and improved oxidative stress. In conclusion, using the type 2 diabetic model, we have successfully shown that HPE not only has a benefit in reducing hyperglycaemia and hyperinsulinaemia, but can also prevent diabetic nephropathy. HPE has the potential to act as an adjuvant for diabetic therapy, and deserves further investigation.

Metal-free oxidative coupling of amines is achieved simply by heating their dimethyl sulfoxide (DMSO) solution under oxygen as oxidant without any other catalysts or additives, accompanied by the formation of an equimolar amount of dimethyl sulfone (DMSO2). EPR experiments indicate that the reaction proceeds via a radical pathway. DMSO may play a triple role as solvent, radical initiator and co-reductant.

An isothermal titration calorimeter was used to measure the excess molar enthalpies ( H E ) of six binary systems at T = 298.15 K under atmospheric pressure. The systems investigated include (1-hexanol + 2-octanone), (1-octanol + 2-octanone), (1-hexanol + octanoic acid), (1-hexanol + hexanoic acid), {N,N-dimethylformamide (DMF) + hexanoic acid}, and {dimethyl sulfoxide (DMSO) + hexanoic acid}. The values of excess molar enthalpies are all positive except for the DMSO- and the DMF-containing systems. In the 1-hexanol with hexanoic acid or octanoic acid systems, the maximum values of H E are located around the mole fraction of 0.4 of 1-hexanol, but the H E vary nearly symmetrically with composition for other four systems. In addition to the modified Redlich–Kister and the NRTL models, the Peng–Robinson (PR) and the Patel–Teja (PT) equations of state were used to correlate the excess molar enthalpy data. The modified Redlich–Kister equation correlates the H E data to within about experimental uncertainty. The calculated results from the PR and the PT are comparable. It is indicated that the overall average absolute relative deviations ( AARD ) of the excess enthalpy calculations are reduced from 18.8% and 18.8% to 6.6% and 7.0%, respectively, as the second adjustable binary interaction parameter, k bij , is added in the PR and the PT equations. Also, the NRTL model correlates the H E data to an overall AARD of 10.8% by using two adjustable model parameters.

A highly enantioselective Rh(I)-catalyzed intramolecular [3 + 2] cycloaddition of 1-yne-VCPs to bicyclo[3.3.0] compounds with an all-carbon chiral quaternary stereocenter at the bridgehead carbon was developed. DFT calculations of the energy surface of the catalytic cycle (complexation, cyclopropane cleavage, alkyne insertion, and reductive elimination) of the asymmetric [3 + 2] cycloaddition reaction indicated that the rate- and stereo-determining step is the alkyne-insertion step. Analysis of the alkyne-insertion transition states revealed that the serious steric repulsion between the substituents in the alkyne moiety of the substrates and the rigid H(8)-BINAP backbone is responsible for not generating the disfavored [3 + 2] cycloadducts.

The kinetic behavior of heterogeneous esterification of acetic acid with methanol over an acidic cation-exchange resin, Amberlyst 36, was investigated by using a packed-bed reactor. The kinetic experiments were conducted at temperatures from 313.15 K to 328.15 K and the molar ratios of methanol to acetic acid in the feed stream from 1 to 5. The reaction rate was found to increase with increasing temperature, but the equilibrium conversions of acetic acid changed slightly over the entire range of reaction temperatures. It is suggested that the heat effect of this reaction is negligible over the experimental conditions. It was also found that the equilibrium conversion of acetic acid increases with the molar ratios of feed increasing from 1 to 5. The relative adsorption strength between any two reacting species was determined from the results of binary adsorption experiments. The magnitude of adsorption strengths follows the order of water > methanol > acetic acid > methyl acetate. The kinetic data were correlated with the ideal-quasi-homogeneous (IQH), the nonideal-quasi-homogeneous (NIQH), the Eley–Rideal (ER), and the Langmuir–Hinshelwood–Hougen–Waston (LHHW) models, respectively, to determine the kinetic parameters. Among these investigated models, the ER and the LHHW are equally well and obviously better than IQH model.

Excess molar enthalpies (HE) of binary mixtures of 2-decanone or dipentyl ether with n-alkanes, including n-dodecane, n-tetradecane, and n-hexadecane, were measured with an isothermal titration calorimeter (ITC) at T = 298.15 K under atmospheric pressure. All the measured HE values are positive over the entire range of composition, indicating that all these mixing processes are endothermic. The HE values varying with composition are found to be nearly symmetric for each binary system. It was also shown that the HE values follow the order of n-hexadecane > n-tetradecane > n-dodecane at a given composition in either the 2-decanone or dipentyl ether binary systems. An empirical Redlich–Kister equation correlated quantitatively these new HE data. The Peng–Robinson and the Patel–Teja equations of state, and the NRTL model were also applied to fit the HE results. Among these tested correlative models, the Patel–Teja equation of state with two adjustable binary interaction parameters generally yielded the best representation.

The liquid–liquid equilibrium (LLE) data, including tie-lines and phase boundaries, were measured for the ternary systems of water + methanol + methyl oleate, water + methanol + methyl linoleate, glycerol + methanol + methyl oleate, and glycerol + methanol + methyl linoleate at temperatures from 298.2 K to 318.2 K under atmospheric pressure. All the LLE data follow the Othmer-Tobias equation. Each ternary system behaves type-I LLE. The areas of two-liquid coexistence region decrease with increasing temperature. The experimental data were applied to test the validity of the UNIFAC model and its modified versions, including UNIFAC-LLE and UNIFAC-Dortmund. The LLE data were also correlated with the NRTL and the UNIQUAC models. The UNIQUAC model yielded better results.

The kinetic behavior of heterogeneous esterification of adipic acid with methanol over acidic cation-exchange resin beads, Amberlyst 35, was investigated through a packed-bed reactor. The experiments were conducted at temperatures from 313.2 K to 343.2 K and the molar ratios of feed (methanol to acid) at 15 and 20. The reaction rate was found to increase with increasing temperature, but the equilibrium conversions of adipic acid were almost identical over the entire temperature range; that is, the heat effect of this reaction system was minor. It was also found that the equilibrium conversion of adipic acid increases slightly as the molar ratio of feed increasing from 15 to 20. The experimental results showed that the mass-transfer resistance could be neglected over the range of experimental conditions. The kinetic data were correlated with two quasi-homogeneous models. The model parameters were determined and their applicability was discussed.

Microwave irradiation was used to accelerate the cyclocondensation of isoflavones and 3-amino-1,2,4-triazoles in the presence of sodium methoxide to produce 6,7-diphenyl[1,2,4]-triazolo[4,3-a]pyrimidines in good to moderate yields.

A novel Rh(I)-catalyzed [(3 + 2) + 1] cycloaddition, which can be regarded as a homologous Pauson-Khand reaction, was developed to synthesize bicyclic cyclohexenones and cyclohexanones, enabling a new approach for synthesis of six-membered carbocycles ubiquitously found in natural products and pharmaceutics. The significance of the Rh-catalyzed [(3 + 2) + 1] cycloaddition has been demonstrated by the total synthesis of a furanoid sesquiterpene natural product, alpha-agarofuran, in which the bicyclic skeleton was constructed by the [(3 + 2) + 1] reaction of 1-yne-VCP and CO.

The kinetic behavior of heterogeneous esterification of propionic acid with methanol over an acidic cation-exchange resin, Amberlyst 36, was investigated by using a fixed-bed reactor. The kinetic experiments were conducted at temperatures from 313.15 to 333.15 K, and molar ratios of methanol to propionic acid in the feed stream from 1 to 5. The reaction rate was found to increase with increasing temperature, but the equilibrium conversions of propionic acid changed only slightly over the entire range of reaction temperatures indicating that the heat effect of this reaction is minor. It was also found that the equilibrium conversion of propionic acid increases with the molar ratios of feed increasing from 1 to 5. The relative adsorption strength between any two reacting species was determined from the results of binary adsorption experiments. The magnitude of adsorption strengths follows the order of water > methyl propionate > propionic acid > methanol. The kinetic data were correlated with the ideal-quas...

The liquid-liquid equilibrium (LLE) phase boundaries were determined experimentally for the ternary systems containing refined sunflower oil, methanol, and one of ten potential cosolvents at 308.2 K under atmospheric pressure by using cloud point method. n-Butylamine was found to be one of the best cosolvents, which could substantially enhance the miscibility between the oil and methanol. The LLE measurements were then extended to the ternary systems of methanol + refined sunflower oil, soybean oil, or canola oil in the presence of the auxiliary cosolvent n-butylamine at temperatures from 298.2 K to 318.2 K. The LLE data were utilized for estimating the model parameters of the NRTL and the UNIQUAC, respectively. In general, these two models can reasonably represent the LLE phase boundaries. Methanol (99.9 %), acetone (99.5 %), dimethyl carbonate (DMC, 99 %), ethyl acetate (99.5 %), methyl acetate (99.5 %), methyl ethyl ketone (MEK, 99 %), methyl propionate (98 %), n-butylamine (99 %), tetrahydrofuran (THF, 99.5 %), and glycerol (99 %) were purchased from Acros, USA. Propylene glycol monomethyl ether acetate (98+ %) was supplied by Aldrich, USA. Methyl tert-butyl ether (99 %) was provided from Fluka, USA and the refined vegetable oils were from domestic edible oil companies. These chemi- cals were used without further purification. The purity levels of the organic solvents have been confirmed with chroma- tographic analysis.

Densities were measured with a high-pressure densitometer for two binary oligomeric systems of poly(ethylene glycol mono-4-octylphenyl ether) (PEGOPE) with 1-octanol or acetophenone at temperatures from 298.15 K to 348.15 K and pressures up to 50 MPa. While the excess volumes are negative in (acetophenone + PEGOPE) over the entire composition range, those are found to change from positive to negative with increasing mole fraction of the solvent in (1-octanol + PEGOPE). The pressure-effect on the liquid densities can be represented accurately by the Tait equation. Moreover, an empirical equation with two characteristic parameters correlates well the PVT data over the entire experimental conditions for each binary system. The experimental specific volumes were also correlated with the Flory–Orwoll–Vrij (FOV) and the Schotte equations of state to within the experimental uncertainty.

To compare the counteracting effects of methylamines trimethylamine N-oxide (TMAO) and betaine on the actions of urea, we have determined the apparent transfer free energies (Δ G ′ tr ) of zwitterionic glycine peptides: glycine (Gly), diglycine (Gly 2 ), triglycine (Gly 3 ), and tetraglycine (Gly 4 ) from water to methylamine and urea, and also the blends of methylamine and urea at a 1:2 ratio as well as various urea concentrations (0.5–8 M) in the presence of 1 M methylamine. The Δ G ′ tr values of the blends of methylamine with urea revealed that the methylamine strongly counteracted the urea actions on glycine peptides. However, the methylamine partially counteracted the deleterious effects of urea on the Gly 4 in the cases of higher urea concentrations (4–8 M) in the presence of 1 M methylamine. The experimental results were further used to estimate the transfer free energies (Δ g ′ tr ) of the peptide backbone unit (–CH 2 C ONH–) contributions.

An isothermal titration calorimeter was used to measure the excess molar enthalpies (HE) of binary systems of 2-octanone or 3-octanone with dodecane, tetradecane, or hexadecane at 298.15 K under atmospheric pressure. The excess molar enthalpies are all positive and vary nearly symmetrically with the mole fraction of the ketones. The maximum values of the excess enthalpies increase with increasing chain length of n-alkanes for the systems containing a given ketone. In addition to a modified Redlich−Kister equation, the Peng−Robinson (PR), the Patel−Teja (PT), and two versions of the Cubic Chain-of-Rotators (CCOR) equations of state were used to correlate the excess molar enthalpies, respectively. The correlated results from the modified Redlich−Kister equation were in good agreement with the experimental values, while the CCOR equation of state with two binary interaction parameters yielded better results than those from other equations of state. The excess molar enthalpy data were also correlated with the...

Excess molar volumes (VE) and ultrasonic studies at T = 303.15 K and atmospheric pressure have been measured over the whole composition range for the binary mixtures of N-methyl-2-pyrrolidone (NMP) with ketones. The ketones studied in the present investigation include methyl ethyl ketone (MEK), diethylketone (DEK), methyl propyl ketone (MPK), methyl isobutyl ketone (MIBK), and cyclohexanone (CH). The VE values were measured using a dilatometer and were negative over the entire mole fraction range for NMP with MEK, DEK, MPK, and MIBK and were positive for NMP with CH. The ultrasonic sound velocities for the above systems were measured with a single crystal interferometer at a frequency of 3 MHz. The sound velocity (u) results have been used to calculate isentropic compressibility (Ks) and deviation in isentropic compressibility (ΔKs) over the entire range of volume fraction. The sound velocity results have been predicted in terms of free length theory (FLT), collision factor theory (CFT), and Nomoto relation. The results reveal that all the theories gave a satisfactory estimate of the sound velocity. The deviation values of the isentropic compressibilities (ΔKs) were negative over the entire range of volume fraction in all the binary liquid mixtures except in the binary system NMP with CH, where we observed positive ΔKs values. The results are interpreted on possible molecular interactions between components.

The (vapour + liquid) equilibrium (VLE) and boiling temperature measurements have been determined at 95.3 kPa as a function of composition for the binary liquid mixtures of N -methyl-2-pyrrolidone (NMP) with branched alcohols using a Swietoslawski-ebulliometer. The branched alcohols include 2-propanol, 2-butanol, 2-methyl-l- propanol, 2-methyl-2-propanol, and 3-methyl-l-butanol. The experimental temperature-composition ( T – x ) results were used to estimate Wilson parameters and then used to calculate the equilibrium vapour compositions and the excess Gibbs free energy at T = 298.15 K. The experimental temperature-composition ( T , x ) results were correlated with the Wilson, the NRTL and the UNIQUAC models. The experimental results are interpreted in terms of intermolecular interactions between constituent molecules.

Dissolution of 1,5-diaminobromo-4,8-dihydroxyanthraquinone (C.I. Disperse Blue 56) in supercritical carbon dioxide was investigated at 393.15 K and 30 MPa over a wide range of contact times. Saturated solubility data of the disperse dyestuff in supercritical carbon dioxide with or without cosolvent were also measured at temperatures from (353.15 to 393.15) K and pressures up to 30 MPa. Either ethanol or dimethyl sulfoxide (DMSO) was used as a cosolvent. The experimental results showed that the equilibrium solubility can be effectively enhanced in the presence of both cosolvents. DMSO was found to yield higher solubility enhancement. The saturated solubility data were correlated with the Charstil and the Mendez-Santiago and Teja models. These two models correlated the solubility data to about within the experimental uncertainty.

Isobaric vapor–liquid equilibrium (VLE) data were measured for the binary mixtures of acetic acid + methyl propionate, propionic acid + methyl acetate, propionic acid + methyl propionate, and methyl propionate + methyl acetate in a temperature range of 330.05–413.15 K at 101.3 kPa. Isothermal vapor–liquid–liquid equilibrium (VLLE) data were also measured for water + methyl acetate + methyl propionate over a pressure range of 43.7–157.0 kPa at 323.24 and 343.15 K. The NRTL-HOC and the UNIQUAC-HOC models with the model parameters determined from the phase equilibrium data of the constituent binaries were applied to predict the VLLE properties for water + methyl acetate + methyl propionate. The validity of the prediction from the UNIFAC-HOC and the UNIFAC-Lyngby-HOC was also tested with the ternary VLLE data. Additionally, the best-fitted values of the six binary parameters of the UNIQUAC-HOC were determined, simultaneously, from the isothermal VLLE ternary data as well.

Vapor−liquid−liquid equilibrium (VLLE) properties were measured with a static apparatus for mixtures of water + methyl acetate, water + methyl propionate, water + methyl acetate + methanol, and wat...

A sensitivity study is performed to examine the impact of lateral boundary conditions (LBCs) on the NOAA-EPA operational Air Quality Forecast Guidance over continental USA. We examined six LBCS: the fixed profile LBC, three global LBCs, and two ozonesonde LBCs for summer 2006. The simulated results from these six runs are compared to IONS ozonesonde and surface ozone measurements from August 1 to 5, 2006. The choice of LBCs can affect the ozone prediction throughout the domain, and mainly influence the predictions in upper altitude or near inflow boundaries, such as the US west coast and the northern border. Statistical results shows that the use of global model predictions for LBCs could improve the correlation coefficients of surface ozone prediction over the US west coast, but could also increase the ozone mean bias in most regions of the domain depending on global models. In this study, the use of the MOZART (Model for Ozone And Related chemical Tracers) prediction for CMAQ (Community Multiscale Air Quality) LBC shows a better surface ozone prediction than that with fixed LBC, especially over the US west coast. The LBCs derived from ozonesonde measurements yielded better O3 correlations in the upper troposphere.

A visual and volume-variable high-pressure phase equilibrium analyzer (PEA) was used for measuring the isothermal vapor−liquid equilibrium (VLE) phase boundaries of CO2 + ethanol and CO2 + acetone at temperatures from (291.15 to 313.15) K over a wide composition range. The isothermal phase equilibrium properties obtained from this work were compared with literature values to clarify the inconsistency of the VLE data taken from different sources. The new VLE data were correlated with the Soave−Redlich−Kwong, the Peng−Robinson, and the Patel−Teja equations of state incorporating with the one-parameter and the two-parameter van der Waals one-fluid mixing rules, respectively.

Dissolution of C.I. Disperse Violet 1 with supercritical carbon dioxide was investigated at 393.2 K and 30 MPa over a wide range of contact times. Saturated solubility data of the disperse dyestuff in supercritical carbon dioxide with or without cosolvent were also measured at temperatures from (353.2 to 393.2) K and pressures up to 30 MPa. Either ethanol or dimethyl sulfoxide (DMSO) was used as a cosolvent. As evidenced from the experimental results, the equilibrium solubility can be effectively enhanced in the presence of both cosolvents. DMSO was found to yield greater solubility enhancement. The saturated solubility data were correlated with the Charstil and the Mendez−Santiago and Teja models. The Chrastil model correlated the solubility data to about within the experimental uncertainty. The correlated results from the Mendez−Santiago−Teja model showed that the solubility data were consistent.

A new visual and volume-variable high-pressure phase equilibrium analyzer (PEA) was installed for determining the vapor–liquid phase boundaries over a wide pressure range, including near critical region, by a synthetic method. This apparatus was tested with the measurement of CO 2 + 1-octanol. The PEA was also utilized to measure the isothermal vapor–liquid phase boundaries of CO 2 + dimethyl sulfoxide, CO 2 + propylene glycol monomethyl ether acetate, and CO 2 + quinoline at temperatures from 308.15 to 358.15 K and pressures up to 28 MPa or near critical pressures. These phase boundary data were correlated with the Soave, the Peng–Robinson and the Patel–Teja equations of state, respectively.