Synthesis of tetrahydrochromenes and dihydronaphthofurans via a cascade process of [3 + 3] and [3 + 2] annulation reactions: mechanistic insight for 6-endo-trig and 5-exo-trig cyclisation.

Substituted tetrahydrochromenes and dihydronaphthofurans are easily accessible by the treatment of ß-tetralone with trans-ß-nitro styrene derived Morita-Baylis-Hillman (MBH) acetates through a formal [3 + 3]/[3 + 2] annulation. The reaction proceeds through a cascade Michael/oxa-Michael pathway with moderate to good yields. A DFT study was carried out to account for the formation of the corresponding six and five-membered heterocycles via 6-endo-trig and 5-exo-trig cyclization.

Investigation of Product Formation in the O(1D, 3P) + N2O Reactions: Comparison of Experimental and Theoretical Kinetics.

The spin-forbidden and spin-allowed reactions of the excited and ground electronic state O(1D, 3P) + N2O(X1Σ+) systems have been studied theoretically. Quantum calculations at the UCCSD(T)/CBS(T, Q, 5)//CCSD/aug-cc-pVTZ level have located two crossing points, MSX1 and MSX2, with energies of 11.2 and 22.7 kcal mol-1 above O(3P) + N2O, respectively. The second-order P-independent rate constants for the adiabatic and non-adiabatic thermal reactions predicted by adiabatic TST/VTST and non-adiabatic TST, respectively, agree closely with the available literature results. The second-order rate constant, k2a = 9.55 × 10-11 exp(-26.09 kcal mol-1/RT) cm3 molecule-1 s-1, for the O(3P) + N2O → 2NO reaction, contributed by both the dominant MSX2 and the minor TS1-a channels, is in reasonable accord with prior experiments and recommendations, covering the temperature range of 1200-4100 K. The calculated rate constant, k2b = 4.47 × 10-12 exp(-12.9 kcal mol-1/RT) cm3 molecule-1 s-1, for the O(3P) + N2O → N2 + O2(a1Δg) reaction, occurring exclusively via MSX1, is also in good agreement with the combined experimental data measured in a shock tube study at T = 1940-3340 K (ref 16) and the result measured by Fourier transform infrared spectroscopy in the temperature range of 988-1083 K (ref 17). Moreover, the spin-allowed rate constants predicted for the singlet-state reactions, k1a = (7.06-7.46) × 10-11 cm3 molecule-1 s-1 for O(1D) + N2O → 2NO and k1b = (4.36-4.66) × 10-11 cm3 molecule-1 s-1 for O(1D) + N2O → N2 + O2(a1Δg) in the temperature range of 200-350 K, agree quantitatively with the experimentally measured data, while the total rate constant k1 = k1a + k1b was also found to be in excellent accordance with many reported values.

Intravenous tissue plasminogen activator for acute ischemic stroke in patients with renal dysfunction.

OBJECTIVE: This study used the Taiwan Stroke Registry data to evaluate the efficacy and safety of intravenous tissue plasminogen activator (tPA) in treating acute ischemic stroke in patients with renal dysfunction. DESIGN: We identified 3525 ischemic stroke patients and classified them into two groups according to the estimated glomerular filtration rate (eGFR) at the emergency department: ≥60, and <60 ml/min/1.73 m2 or on dialysis and by the propensity score from August 2006 to May 2015. The odds ratio of poor functional outcome (modified Rankin Scale ≥2) was calculated for patients with tPA treatment (N = 705), compared to those without tPA treatment (N = 2820), by eGFR levels, at 1, 3 and 6 months after ischemic stroke. We also evaluated the risks of intracerebral hemorrhage, upper gastrointestinal bleeding, mortality, between the two groups by eGFR levels. RESULTS: Among patients with eGFR levels of <60 ml/min/1.73 m2, tPA therapy reduced the odds ratio of poor functional outcome to 0.60 (95% confidence interval = 0.42-0.87) at 6 months after ischemic stroke. The tPA therapy was not associated with increased overall risk of upper gastrointestinal bleeding, but with increased risk of intracerebral hemorrhage. The low eGFR was not a significant risk factor of intracerebral hemorrhage among ischemic stroke patients receiving tPA treatment. CONCLUSIONS: tPA for acute ischemic stroke could improve functional outcomes without increasing the risks of upper gastrointestinal bleeding for patients with or without renal dysfunction. The low eGFR was not a significant risk factor for intracerebral hemorrhage among patients receiving tPA treatment.

Increased incidence and recurrence rates of acute diverticulitis in patients with irritable bowel syndrome.

AIM: Acute diverticulitis (AD) is commonly diagnosed in outpatient and emergency departments and is associated with severe complications such as perforation and fistula. Symptoms of irritable bowel syndrome (IBS), such as abdominal pain, constipation and diarrhoea, are also common with AD. This study aimed to evaluate the strength of a possible association between IBS and AD. METHOD: This retrospective study analysed records from Taiwan's National Health Insurance Research Database and involved a total of 25 810 patients, including 12 905 IBS patients diagnosed between 2000 and 2012. The IBS and non-IBS cohorts were matched by propensity score for age, gender, comorbidities and medication, then compared for confounding variables by the chi-square test or Student's t-test. The association between AD and IBS was determined using Cox proportional hazards models. Kaplan-Meier curves assessed the cumulative incidence of AD in IBS patients. RESULTS: The overall incidence of AD was 3.95-fold higher in the IBS cohort than in the non-IBS cohort (63.34 vs 16.02 per 100 000 person-years, respectively) and IBS was an independent risk factor for subsequent diagnosis of AD in multivariate Cox proportional hazards regression model adjusted hazards ratio (aHR = 3.84, 95% CI = 2.29-6.44, P < 0.001) and Kaplan-Meier (log-rank test, P < 0.001) analysis. IBS was also associated with a high recurrence rate of AD (aHR = 8.30, 95% CI = 1.07-64.30, P = 0.04). CONCLUSION: The epidemiological evidence in this study demonstrates that patients with IBS are associated with a higher incidence of AD and also its recurrence.

Retrospective analysis of the association between tooth loss and dementia: a population-based matched case-control study.

OBJECTIVE: To clarify the association between multiple tooth loss and dementia. BASIC RESEARCH DESIGN: Case-control study based on the claims data from National Health Insurance Research Database (NHIRD). Patients were divided into two groups: the dementia groups and non-dementia group. For each case patient, one control patient was randomly selected and frequency matched by age (per 5 years) and sex. The case group comprised patients newly diagnosed with dementia, and the index date was the the date of dementia diagnosis, which became the baseline for comorbidity and age calculations. RESULTS: Among the 43,026 individuals, patients with dementia had a significantly higher extraction density at ages 60-69 (p ⟨ 0.0001) and 70-79 (p = 0.04) years compared with control patients. CONCLUSIONS: This population-based retrospective study demonstrated an association between tooth loss and dementia. Patients in Taiwan with more tooth extraction experience are likely to have an increased risk of dementia.

Potassium-Presenting Zinc Oxide Surfaces Induce Vertical Phase Separation in Fullerene-Free Organic Photovoltaics.

Bulk heterojunction (BHJ) structure based organic photovoltaics (OPVs) have recently showed great potential for achieving high power conversion efficiencies (PCEs). An ideal BHJ structure would feature large donor/acceptor interfacial areas for efficient exciton dissociation and gradient distributions with high donor and acceptor concentrations near the anode and cathode, respectively, for efficient charge extraction. However, the random mixing of donors and acceptors in the BHJ often suffers the severe charge recombination in the interface, resulting in poor charge extraction. Herein, we propose a new approach-treating the surface of the zinc oxide (ZnO) as an electron transport layer with potassium hydroxide-to induce vertical phase separation of an active layer incorporating the nonfullerene acceptor IT-4F. Density functional theory calculations suggested that the binding energy difference between IT-4F and the PBDB-T-2Cl, to the potassium (K)-presenting ZnO interface, is twice as strong as that for IT-4F and PBDB-T-2Cl to the untreated ZnO surface, such that it would induce more IT-4F moving toward the K-presenting ZnO interface than the untreated ZnO interface thermodynamically. Benefiting from efficient charge extraction, the best PCEs increased to 12.8% from 11.8% for PBDB-T-2Cl:IT-4F-based devices, to 12.6% from 11.6% for PBDB-T-2Cl:Y1-4F-based devices, to 13.5% from 12.2% for PBDB-T-2Cl:Y6-based devices, and to 15.7% from 15.1% for PM6:Y6-based devices.

Computational Study on the Mechanisms and Rate Constants for the O(3P,1D) + OCS Reactions.

The mechanisms and kinetics of O(3P,1D) + OCS(X1Σ+) reactions have been studied by the high-level G2M(CC2) and CCSD(T)/6-311+G(3df)//B3LYP/6-311+G(3df) methods in conjunction with the transition-state theory and variational Rice-Ramsperger-Kassel-Marcus theory calculations. The result shows that the triplet surface proceeds directly by abstraction and substitution channels to produce SO(3P) + CO(X1Σ+) and S(3P) + CO2(X1 Σg+) by passing the barriers of 7.6 and 9.1 kcal·mol-1 at the G2M(CC2)//B3LYP/6-311+G(3df) level, respectively, while two stable intermediates, LM1 (OSCO1) and LM2 (SC(O)O1), are formed barrierlessly from O(1D) + OCS(X1Σ+) in the singlet surface, which lie at -40.5 and -50.1 kcal·mol-1 relative to O(3P) + OCS(X1Σ+) reactants and decompose to CO(X1Σ+) + SO(a1Δ) and S(1D) + CO2(X1Σg+). LM1 and LM2 may also be produced by singlet-triplet surface crossings via MSX1 and MSX2; the predicted total rate constant for the O(3P) + OCS(X1Σ+) reaction including the crossings, 9.2 × 10-11 exp(-5.18 kcal·mol-1/RT) cm3 molecule-1 s-1, is in good agreement with available experimental data. The branching ratio of the CO2 product channel, 0.22-0.32, between 1200 and 1600 K, is also in excellent agreement with the value of 0.2-0.3 measured by Isshiki et al. (J. Phys. Chem. A. 2003, 107, 2464).

Infrared Emission from Photodissociation of Methyl Formate [HC(O)OCH3] at 248 and 193 nm: Absence of Roaming Signature.

Following photodissociation at 248 nm of gaseous methyl formate (HC(O)OCH3, 0.73 Torr) and Ar (0.14 Torr), temporally resolved vibration-rotational emission spectra of highly internally excited CO (ν ≤ 11, J ≤ 27) in the 1850-2250 cm-1 region were recorded with a step-scan Fourier-transform spectrometer. The vibration-rotational distribution of CO is almost Boltzmann, with a nascent average rotational energy (ER0) of 3 ± 1 kJ mol-1 and a vibrational energy (EV0) of 76 ± 9 kJ mol-1. With 3 Torr of Ar added to the system, the average vibrational energy was decreased to EV0 = 61 ± 7 kJ mol-1. We observed no distinct evidence of a bimodal rotational distribution for ν = 1 and 2, as reported previously [Lombardi et al., J. Phys. Chem. A 2016, 129, 5155], as evidence of a roaming mechanism. The vibrational distribution with a temperature of ∼13000 ± 1000 K, however, agrees satisfactorily with trajectory calculations of these authors, who took into account conical intersections from the S1 state. Highly internally excited CH3OH that is expected to be produced from a roaming mechanism was unobserved. Following photodissociation at 193 nm of gaseous HC(O)OCH3 (0.42 Torr) and Ar (0.09 Torr), vibration-rotational emission spectra of CO (ν ≤ 4, J ≤ 38) and CO2 (with two components of varied internal distributions) were observed, indicating that new channels are open. Quantum-chemical calculations, computed at varied levels of theory, on the ground electronic potential-energy schemes provide a possible explanation for some of our observations. At 193 nm, the CO2 was produced from secondary dissociation of the products HC(O)O and CH3OCO, and CO was produced primarily from secondary dissociation of the product HCO produced on the S1 surface or the decomposition to CH3OH + CO on the S0 surface.

Carbon-doped SnS2 nanostructure as a high-efficiency solar fuel catalyst under visible light.

Photocatalytic formation of hydrocarbons using solar energy via artificial photosynthesis is a highly desirable renewable-energy source for replacing conventional fossil fuels. Using an L-cysteine-based hydrothermal process, here we synthesize a carbon-doped SnS2 (SnS2-C) metal dichalcogenide nanostructure, which exhibits a highly active and selective photocatalytic conversion of CO2 to hydrocarbons under visible-light. The interstitial carbon doping induced microstrain in the SnS2 lattice, resulting in different photophysical properties as compared with undoped SnS2. This SnS2-C photocatalyst significantly enhances the CO2 reduction activity under visible light, attaining a photochemical quantum efficiency of above 0.7%. The SnS2-C photocatalyst represents an important contribution towards high quantum efficiency artificial photosynthesis based on gas phase photocatalytic CO2 reduction under visible light, where the in situ carbon-doped SnS2 nanostructure improves the stability and the light harvesting and charge separation efficiency, and significantly enhances the photocatalytic activity.

Ni-Nanocluster Modified Black TiO2 with Dual Active Sites for Selective Photocatalytic CO2 Reduction.

One of the key challenges in artificial photosynthesis is to design a photocatalyst that can bind and activate the CO2 molecule with the smallest possible activation energy and produce selective hydrocarbon products. In this contribution, a combined experimental and computational study on Ni-nanocluster loaded black TiO2 (Ni/TiO2[Vo] ) with built-in dual active sites for selective photocatalytic CO2 conversion is reported. The findings reveal that the synergistic effects of deliberately induced Ni nanoclusters and oxygen vacancies provide (1) energetically stable CO2 binding sites with the lowest activation energy (0.08 eV), (2) highly reactive sites, (3) a fast electron transfer pathway, and (4) enhanced light harvesting by lowering the bandgap. The Ni/TiO2[Vo] photocatalyst has demonstrated highly selective and enhanced photocatalytic activity of more than 18 times higher solar fuel production than the commercial TiO2 (P-25). An insight into the mechanisms of interfacial charge transfer and product formation is explored.

EZH2-mediated upregulation of ROS1 oncogene promotes oral cancer metastasis.

Current anti-epidermal growth factor receptor (EGFR) therapy for oral cancer does not provide satisfactory efficacy due to drug resistance or reduced EGFR level. As an alternative candidate target for therapy, here we identified an oncogene, ROS1, as an important driver for oral squamous cell carcinoma (OSCC) metastasis. Among tumors from 188 oral cancer patients, upregulated ROS1 expression strongly correlated with metastasis to lung and lymph nodes. Mechanistic studies uncover that the activated ROS1 results from highly expressed ROS1 gene instead of gene rearrangement, a phenomenon distinct from other cancers. Our data further reveal a novel mechanism that reduced histone methyltransferase EZH2 leads to a lower trimethylation of histone H3 lysine 27 suppressive modification, relaxes chromatin, and promotes the accessibility of the transcription factor STAT1 to the enhancer and the intron regions of ROS1 target genes, CXCL1 and GLI1, for upregulating their expressions. Down-regulation of ROS1 in highly invasive OSCC cells, nevertheless, reduces cell proliferation and inhibits metastasis to lung in the tail-vein injection and the oral cavity xenograft models. Our findings highlight ROS1 as a candidate biomarker and therapeutic target for OSCC. Finally, we demonstrate that co-targeting of ROS1 and EGFR could potentially offer an effective oral cancer therapy.

GATA3 interacts with and stabilizes HIF-1α to enhance cancer cell invasiveness.

This corrects the article DOI: 10.1038/onc.2017.8.

Computational Chemical Kinetics for the Reaction of Criegee Intermediate CH2OO with HNO3 and Its Catalytic Conversion to OH and HCO.

The kinetics and mechanisms for the reaction of the Criegee intermediate CH2OO with HNO3 and the unimolecular decomposition of its reaction product CH2(O)NO3 are important in atmospheric chemistry. The potential-energy profile of the reactions predicted with the CCSD(T)/aug-cc-pVTZ//B3LYP/aug-cc-pVTZ method shows that the initial association yields a prereaction complex that isomerizes by H migration to yield excited intermediate nitrooxymethyl hydroperoxide NO3CH2OOH* with internal energy ∼44 kcal mol-1. A fragmentation of this excited intermediate produces CH2(O)NO3 + OH with its transition state located 5.0 kcal mol-1 below that of the reactants. Further decomposition of CH2(O)NO3 produces HCO + HNO3, forming a catalytic cycle for destruction of CH2OO by HNO3. The rate coefficients and product-branching ratios were calculated in the temperature range 250-700 K at pressure 20-760 Torr (N2) using the variational-transition-state and Rice-Ramsperger-Kassel-Marcus (RRKM) theories. The predicted total rate coefficient for reaction CH2OO + HNO3 at 295 K, 5.1 × 10-10 cm3 molecule-1 s-1, agrees satisfactorily with the experimental value, (5.4 ± 1.0) × 10-10 cm3 molecule-1 s-1. The predicted branching ratios at 295 K are 0.21 for the formation of NO3CH2OOH and 0.79 for CH2(O)NO3 + OH at a pressure of 40 Torr (N2), and 0.79 for the formation of NO3CH2OOH and 0.21 for CH2(O)NO3 + OH at 760 Torr (N2). This new catalytic conversion of CH2OO to HCO + OH by HNO3 might have significant impact on atmospheric chemistry.

GATA3 interacts with and stabilizes HIF-1α to enhance cancer cell invasiveness.

GATA binding protein 3 (GATA3) is indispensable in development of human organs. However, the role of GATA3 in cancers remains elusive. Hypoxia inducible factor (HIF)-1 plays an important role in pathogenesis of human cancers. Regulation of HIF-1α degradation is orchestrated through collaboration of its interacting proteins. In this study, we discover that GATA3 is upregulated in head and neck squamous cell carcinoma (HNSCC) and is an independent predictor for poor disease-free survival. GATA3 promotes invasive behaviours of HNSCC and melanoma cells in vitro and in immunodeficient mice. Mechanistically, GATA3 physically associates with HIF-1α under hypoxia to inhibit ubiquitination and proteasomal degradation of HIF-1α, which is independent of HIF-1α prolyl hydroxylation. Chromatin immunoprecipitation assays show that the GATA3/HIF-1α complex binds to and regulates HIF-1 target genes, which is also supported by the microarray analysis. Notably, the GATA3-mediated invasiveness can be significantly reversed by HIF-1α knockdown, suggesting a critical role of HIF-1α in the underlying mechanism of GATA3-mediated effects. Our findings suggest that GATA3 stabilizes HIF-1α to enhance cancer invasiveness under hypoxia and support the GATA3/HIF-1α axis as a potential therapeutic target for cancer treatment.

Pressure drop of two-phase helium along long cryogenic flexible transfer lines to support a superconducting RF operation at its cryogenic test stand.

BACKGROUND: Establishing a stand-alone cryogenic test stand is of vital importance to ensure the highly reliable and available operation of superconducting radio-frequency module in a synchrotron light source. Operating a cryogenic test stand relies strongly on a capability to deliver two-phase helium along long cryogenic transfer lines. A newly constructed cryogenic test stand with flexible cryogenic transfer lines of length 220 m at National Synchrotron Radiation Research Center is required to support a superconducting radio-frequency module operated at 126.0 kPa with a 40-W dynamic load for a long-term reliability test over weeks. It is designed based on a simple analytical approach with the introduction of a so-called tolerance factor that serves to estimate the pressure drops in transferring a two-phase helium flow with a substantial transfer cryogenic heat load. Tolerance factor 1.5 is adopted based on safety factor 1.5 commonly applied in cryogenic designs to estimate the total mass flow rate of liquid helium demanded. A maximum 60-W dynamic load is verified with experiment measured with heater power 60 W instead after the cryogenic test stand has been installed. RESULTS: Aligning the modeled cryogenic accumulated static heat load with the results measured in situ, actual tolerance factor 1.287 is obtained. The feasibility and validity of our simple analytical approach with actual tolerance factor 1.287 have been scrutinized by using five test cases with varied operating conditions. Calculated results show the discrepancies of the pressure drops between the estimated and measured values for both liquid helium and cold gaseous helium transfer lines have an underestimate 0.11 kPa and an overestimate 0.09 kPa, respectively. A discrepancy is foreseen, but remains acceptable for engineering applications from a practical point of view. CONCLUSIONS: The simple analytical approach with the introduction of a tolerance factor can provide not only insight into optimizing the choice of each lossy cryogenic piping element of the transfer lines in the design phase but also firm guidance for upgrading the present cryogenic transfer lines for its subsequent application.

Quantum chemical investigation on the role of Li adsorbed on anatase (101) surface nano-materials on the storage of molecular hydrogen.

Lithiation of TiO2 has been shown to enhance the storage of hydrogen up to 5.6 wt% (Hu et al. J Am Chem Soc 128:11740-11741, 2006). The mechanism for the process is still unknown. In this work we have carried out a study on the adsorption and diffusion of Li atoms on the surface and migration into subsurface layers of anatase (101) by periodic density functional theory calculations implementing on-site Coulomb interactions (DFT+U). The model consists of 24 [TiO2] units with 11.097 × 7.655 Å(2) surface area. Adsorption energies have been calculated for different Li atoms (1-14) on the surface. A maximum of 13 Li atoms can be accommodated on the surface at two bridged O, Ti-O, and Ti atom adsorption sites, with 83 kcal mol(-1) adsorption energy for a single Li atom adsorbed between two bridged O atoms from where it can migrate into the subsurface layer with 27 kcal mol(-1) energy barrier. The predicted adsorption energies for H2 on the lithiated TiO2 (101) surface with 1-10 Li atoms revealed that the highest adsorption energies occurred on 1-Li, 5-Li, and 9-Li surfaces with 3.5, 4.4, and 7.6 kcal mol(-1), respectively. The values decrease rapidly with additional H2 co-adsorbed on the lithiated surfaces; the maximum H2 adsorption on the 9Li-TiO2(a) surface was estimated to be only 0.32 wt% under 100 atm H2 pressure at 77 K. The result of Bader charge analysis indicated that the reduction of Ti occurred depending on the Li atoms covered on the TiO2 surface.

A novel and facile decay path of Criegee intermediates by intramolecular insertion reactions via roaming transition states.

We have discovered a new and highly competitive product channel in the unimolecular decay process for small Criegee intermediates, CH2OO and anti/syn-CH3C(H)OO, occurring by intramolecular insertion reactions via a roaming-like transition state (TS) based on quantum-chemical calculations. Our results show that in the decomposition of CH2OO and anti-CH3C(H)OO, the predominant paths directly produce cis-HC(O)OH and syn-CH3C(O)OH acids with >110 kcal/mol exothermicities via loose roaming-like insertion TSs involving the terminal O atom and the neighboring C-H bonds. For syn-CH3C(H)OO, the major decomposition channel occurs by abstraction of a H atom from the CH3 group by the terminal O atom producing CH2C(H)O-OH. At 298 K, the intramolecular insertion process in CH2OO was found to be 600 times faster than the commonly assumed ring-closing reaction.