Definitive intensity-modulated radiotherapy or surgery for early oral cavity squamous cell carcinoma: Propensity-score-matched, nationwide, population-based cohort study.

BACKGROUND: No evidence is currently available to estimate the outcomes of intensity-modulated radiation therapy (IMRT) and surgery for patients with early oral cavity squamous cell carcinoma (E-OCSCC). METHODS: We recruited patients from the Taiwan Cancer Registry Database who had received a diagnosis of E-OCSCC. Propensity score matching was performed, and Cox proportional hazards model was used to analyze all-cause mortality. RESULTS: In the multivariate Cox regression analyses, the adjusted hazard ratio (aHR) (95% confidence interval [CI]) for surgery compared with definitive IMRT, T2N0M0 compared with T1N0M0, and male patients compared with female patients were 0.303 (0.245, 0.375), 1.340 (1.077, 1.668), and 2.012 (1.432, 2.826), respectively. The aHRs (95% CIs) for age 61 to 70, 71 to 80, and ≧81 years compared with <40 years were 2.984 (1.43, 4.225), 3.353 (2.578, 4.112), and 4.277 (4.104, 5.679), respectively. CONCLUSIONS: For patients with E-OCSCC, surgery may be considered the first option rather than definitive IMRT.

Definitive radiotherapy or surgery for early oral squamous cell carcinoma in old and very old patients: A propensity-score-matched, nationwide, population-based cohort study.

PURPOSE: Although patients aged >70 years are subject to early oral cavity squamous cell carcinoma (E-OCSCC), evidence is currently lacking regarding the probable outcomes of definitive radiotherapy (RT) compared to surgery in this population. METHODS: We recruited patients aged ≥70 years with a diagnosis of E-OCSCC from the Taiwan Cancer Registry Database. Propensity score matching was performed, and Cox proportional-hazards model curves were used to analyze all-cause mortality of patients at different age intervals undergoing different treatments. RESULTS: The matching process yielded a final cohort of 604 patients in the definitive RT and surgery cohorts who were eligible for further analysis. These patients were classified as old (70-80 years) and very old (>80 years). In the multivariate Cox regression analysis, the adjusted hazard ratio (aHR) (95% confidence interval [CI]) for surgery compared with definitive RT was 0.465 (0.354-0.610, P < 0.001). The aHR (95% CI) for age >80 years compared with age 70-80 years was 2.370 (1.720, 3.265, P < 0.001). The aHR (95% CI) for T2N0M0 compared with T1N0M0 was 1.752 (1.321-2.32, P < 0.001). The aHR (95% CI) for Charlson Comorbidity Index (CCI) ≥ 2 compared with CCI = 0 was 1.264 (1.137-1.738, P = 0.011). After stratified analysis, the aHRs for surgery compared with definitive RT were 0.484 (0.352-0.665, P < 0.001) and 0.411 (0.232-0.728, P = 0.002) among old and very old patients with E-OCSCC, respectively. CONCLUSIONS: Surgery may be more beneficial than definitive RT in selected elderly patients with E-OCSCC.

Oligomerization of Light Olefins Catalyzed by Brønsted-Acidic Metal-Organic Framework-808.

Sulfated metal-organic framework-808 (S-MOF-808) exhibits strong Brønsted-acidic character which makes it a potential candidate for the heterogeneous acid catalysis. Here, we report the isomerization and oligomerization reactions of light olefins (C3-C6) over S-MOF-808 at relatively low temperatures and ambient pressure. Different products (dimers, isomers, and heavier oligomers) were obtained for different olefins, and effective C-C coupling was observed between isobutene and isopentene. Among the substrates investigated, facile oligomerization occurred very specifically for the structures with an α-double bond and two substituents at the second carbon atom of the main carbon chain. The possible oligomerization mechanism of light olefins was discussed based on the reactivity and selectivity trends. Moreover, the deactivation and regeneration of S-MOF-808 were investigated. The catalyst deactivates via two mechanisms which predominance depends on the substrate and reaction conditions. Above 110 °C, a loss of acidic sites was observed due to water desorption, and the deactivated catalyst could be regenerated by a simple treatment with water vapor. For C5 substrates and unsaturated ethers, the oligomers with increased molecular weight caused deactivation via blocking of the active sites, which could not be readily reversed. These findings offer the first systematic report on carbocation-mediated olefin coupling within MOFs in which the Brønsted acidity is associated with the secondary building units of the MOF itself and is not related to any guest substance hosted within its pore system.

Association between renin-angiotensin-aldosterone system blockade and future osteoporotic fracture risk in hypertensive population: A population-based cohort study in Taiwan.

Tissue renin-angiotensin-aldosterone system (RAAS) activation in sites of osteoporosis had been demonstrated in animal studies; however, the possibility of RAAS blockade to prevent future osteoporotic fracture had rarely been verified in clinical studies. We Used the Taiwan Longitudinal Health insurance database 2000 to 2008, the cohort study comprised patients age over 40 with a recorded new diagnosis of hypertension between January 1, 2000 to December 31, 2008, in addition, patients who had diagnosis of osteoporosis before the date of cohort enter were excluded. After the definite diagnosis of hypertension, each patient was followed until osteoporotic fracture happened or the end of 2008. The occurrence of osteoporotic fracture was evaluated in patients who either were or without taking RAAS blockade agents. Cox proportional hazard regressions were used to evaluate the osteoporotic fracture incidence after adjusting for known confounding factors. In total, 57,132 hypertensive patients comprised the study cohort. Our study results showed that the incidence of osteoporosis fracture in the whole cohort was significantly higher in the RAAS blockade non-user group than the user group. This phenomenon was observed in both sex and all age categories. Sensitivity analysis further showed the concordant lower osteoporosis fracture risk in patients with various RAAS blockers usage durations; the risk of osteoporosis fracture was the lowest in those drug use >365 days when compared with the non-user cohort. In conclusion, our study result demonstrated the lower future osteoporotic fracture risk in hypertensive subjects who received long term RAAS blocker treatment.

New Insights into Aldol Reactions of Methyl Isocyanoacetate Catalyzed by Heterogenized Homogeneous Catalysts.

The Hayashi-Ito aldol reaction of methyl isocyanoacetate (MI) and benzaldehydes, a classic homogeneous Au(I)-catalyzed reaction, was studied with heterogenized homogeneous catalysts. Among dendrimer encapsulated nanoparticles (NPs) of Au, Pd, Rh, or Pt loaded in mesoporous supports and the homogeneous analogues, the Au NPs led to the highest yield and highest diastereoselectivity of products in toluene at room temperature. The Au catalyst was stable and was recycled for at least six runs without substantial deactivation. Moreover, larger pore sizes of the support and the use of a hydrophobic solvent led to a high selectivity for the trans diastereomer of the product. The activation energy is sensitive to neither the size of Au NPs nor the support. A linear Hammett plot was obtained with a positive slope, suggesting an increased electron density on the carbonyl carbon atom in the rate-limiting step. IR studies revealed a strong interaction between MI and the gold catalyst, supporting the proposed mechanism, in which rate-limiting step involves an electrophilic attack of the aldehyde on the enolate formed from the deprotonated MI.

Association of the Genetic Polymorphisms RRM1 -756T>C and -269C>A With Cervical Neoplasia.

Cervical neoplasia is one of the most prevalent malignant neoplasms worldwide. Ribonucleotide reductase 1 (RRM1) is thought to play an essential role in modulating the development and progression of cervical neoplasia. Two novel genetic polymorphisms, RRM1 -756T>C and -269 C>A, are significantly correlated with RRM1 expression. Some epidemiological studies have demonstrated that genetic variants play a crucial role in susceptibility to cervical cancer. The present study aimed to identify the genetic polymorphisms RRM1 -756T>C and -269 C>A in patients with cervical neoplasia and healthy controls. In total, 493 subjects, comprising 324 healthy controls and 169 patients with cervical neoplasia, were enrolled for this study. The allelic discrimination of the RRM1 -756T>C (rs11030918) and -269C>A (rs12806698) polymorphisms was assessed using the ABI StepOne™ real-time polymerase chain reaction system and analyzed using Software Design Specification (SDS), Version 3.0, software with TaqMan assays. The risk of cervical cancer was examined, revealing adjusted odds ratios and 95% confidence intervals of 1.25 [0.51, 3.08] and 1.09 [0.43, 2.78] for individuals with CC alleles of RRM1 -756T>C and for individuals with AA alleles of RRM1 -269C>A genetic polymorphisms, respectively, compared to individuals with wild-type RRM1 genetic polymorphisms. No significant genetic interaction effect was observed in susceptibility to cervical neoplasia, and no association was found between genetic polymorphisms and clinical statuses of invasive cervical cancer. The genetic polymorphisms RRM1 -756T>C and -269C>A may not be a factor for susceptibility to cervical neoplasia.

Ambient Stable Trigonal Bipyramidal Copper(III) Complexes Equipped with an Exchangeable Axial Ligand.

A stable trigonal bipyramidal copper(III) complex, [PPN][Cu((TMS)PS3)Cl] (1, wherein PPN represents bis(triphenylphosphine)iminium), was synthesized from CuCl2/PPNCl via intramolecular copper(II) disproportionation. Under ambient conditions, the axial chloride of 1 is exchangeable in solution thus making 1 serve as an intermediate to prepare trigonal bipyramidal copper(III) derivatives, e.g., [PPN][Cu((TMS)PS3)(N3)] (2) and [Cu((TMS)PS3)(DABCO)] (3). Diamagnetic complexes 1-3 were fully characterized by X-ray crystallography, NMR, UV-vis, and Cu K-edge absorption spectroscopy. A series of UV-vis titrations were performed to investigate the relative ligand affinity toward the [Cu((TMS)PS3)] moiety, verifying the 1:1 binding equilibrium between various ligands. Compared to known copper(III) compounds, Cu K-edge absorptions of 1-3 possess lower pre-edge energy and higher shakedown transition energy, which, respectively, attribute to the electron donation from (TMS)PS3(3-) ligand and their trigonal ligand field.

Ru nanocrystals with shape-dependent surface-enhanced Raman spectra and catalytic properties: controlled synthesis and DFT calculations.

Despite its multidisciplinary interests and technological importance, the shape control of Ru nanocrystals still remains a great challenge. In this article, we demonstrated a facile hydrothermal approach toward the controlled synthesis of Ru nanocrystals with the assistance of first-principles calculations. For the first time, Ru triangular and irregular nanoplates as well as capped columns with tunable sizes were prepared with high shape selectivity. In consistency with the experimental observations and density functional theory (DFT) calculations confirmed that both the intrinsic characteristics of Ru crystals and the adsorption of certain reaction species were responsible for the shape control of Ru nanocrystals. Ultrathin Ru nanoplates exposed a large portion of (0001) facets due to the lower surface energy of Ru(0001). The selective adsorption of oxalate species on Ru(10-10) would retard the growth of the side planes of the Ru nanocrystals, while the gradual thermolysis of the oxalate species would eliminate their adsorption effects, leading to the shape evolution of Ru nanocrystals from prisms to capped columns. The surface-enhanced Raman spectra (SERS) signals of these Ru nanocrystals with 4-mercaptopyridine as molecular probes showed an enhancement sequence of capped columns > triangle nanoplates > nanospheres, probably due to the sharp corners and edges in the capped columns and nanoplates as well as the shrunk interparticle distance in their assemblies. CO-selective methanation tests on these Ru nanocrystals indicated that the nanoplates and nanospheres had comparable activities, but the former has much better CO selectivity than the latter.

Pt-Cu and Pt-Pd-Cu concave nanocubes with high-index facets and superior electrocatalytic activity.

Pt-Cu nanostructures: Pt-Cu nanocubes (NCs), concave nanocubes (CNCs), and Pt-Pd-Cu CNCs with high-index facets (HIFs) were prepared through progressive galvanic replacements in a one-pot hydrothermal approach. The HIF-enclosed CNCs showed superior activities to (100)-enclosed NC catalysts for methanol oxidations owing to the modification of both the surface electronic structures and the surface atomic arrangements (see figure).

Directed evolution of Streptomyces clavuligerus deacetoxycephalosporin C synthase for enhancement of penicillin G expansion.

The deacetoxycephalosporin C synthase from Streptomyces clavuligerus was directly modified for enhancement of penicillin G expansion into phenylacetyl-7-aminodeacetoxycephalosporanic acid, an important intermediate in the industrial manufacture of cephalosporin antibiotics. Nine new mutants, mutants M73T, T91A, A106T, C155Y, Y184H, M188V, M188I, H244Q, and L277Q with 1.4- to 5.7-fold increases in the kcat/Km ratio, were obtained by screening 6,364 clones after error-prone PCR-based random mutagenesis. Subsequently, DNA shuffling was carried out to screen possible combinations of substitutions, including previous point mutations. One quaternary mutant, the C155Y/Y184H/V275I/C281Y mutant, which had a kcat/Km ratio that was 41-fold higher was found after 10,572 clones were assayed. The distinct mutants obtained using different mutagenesis methods demonstrated the complementarity of the techniques. Interestingly, most of the mutated residues that result in enhanced activities are located within or near the unique small barrel subdomain, suggesting that manipulation of this subdomain may be a constructive strategy for improvement of penicillin expansion. Several mutations had very distinct effects on expansion of penicillins N and G, perhaps due to different penicillin-interacting modes within the enzyme. Thus, the present study provided not only promising enzymes for cephalosporin biosynthesis but also a large number of mutants, which provided new insights into the structure-function relationship of the protein that should lead to further rational engineering.

Engineering Streptomyces clavuligerus deacetoxycephalosporin C synthase for optimal ring expansion activity toward penicillin G.

The deacetoxycephalosporin C synthase (DAOCS) from Streptomyces clavuligerus was engineered with the aim of enhancing the conversion of penicillin G into phenylacetyl-7-aminodeacetoxycephalosporanic acid, a precursor of 7-aminodeacetoxycephalosporanic acid, for industrial application. A single round of random mutagenesis followed by the screening of 5,500 clones identified three mutants, G79E, V275I, and C281Y, that showed a two- to sixfold increase in the k(cat)/K(m) ratio compared to the wild-type enzyme. Site-directed mutagenesis to modify residues surrounding the substrate resulted in three mutants, N304K, I305L, and I305M, with 6- to 14-fold-increased k(cat)/K(m) values. When mutants containing all possible combinations of these six sites were generated to optimize the ring expansion activity for penicillin G, the double mutant, YS67 (V275I, I305M), showed a significant 32-fold increase in the k(cat)/K(m) ratio and a 5-fold increase in relative activity for penicillin G, while the triple mutant, YS81 (V275I, C281Y, I305M), showed an even greater 13-fold increase in relative activity toward penicillin G. Our results demonstrate that this is a robust approach to the modification of DAOCS for an optimized DAOCS-penicillin G reaction.