Isolation of bis(copper) key intermediates in Cu-catalyzed azide-alkyne "click reaction".

The copper-catalyzed 1,3-dipolar cycloaddition of an azide to a terminal alkyne (CuAAC) is one of the most popular chemical transformations, with applications ranging from material to life sciences. However, despite many mechanistic studies, direct observation of key components of the catalytic cycle is still missing. Initially, mononuclear species were thought to be the active catalysts, but later on, dinuclear complexes came to the front. We report the isolation of both a previously postulated π,σ-bis(copper) acetylide and a hitherto never-mentioned bis(metallated) triazole complex. We also demonstrate that although mono- and bis-copper complexes promote the CuAAC reaction, the dinuclear species are involved in the kinetically favored pathway

Prognostic Outcomes and Risk Factors for Patients with Renal Cell Carcinoma and Venous Tumor Thrombus after Radical Nephrectomy and Thrombectomy: The Prognostic Significance of Venous Tumor Thrombus Level.

IntroductionTo evaluate the prognostic outcomes and risk factors for renal cell carcinoma (RCC) patients with venous tumor thrombus in China.Materials and methodsWe reviewed the clinical information of 169 patients who underwent radical nephrectomy and thrombectomy. Overall and cancer-specific survival rates were analyzed. Univariate and multivariate analyses were used to investigate the potential prognostic factors.ResultsThe median survival time was 63 months. The five-year overall survival and cancer-specific survival rate were 53.6% and 54.4% for all patients. For all patients, significant survival difference was only observed between early (below hepatic vein) and advanced (above hepatic vein) tumor thrombus. However, significant differences existed between both RV/IVC and early/advanced tumor thrombus groups in N0M0 patients. Multivariate analysis demonstrated that higher tumor thrombus level (p = 0.016, RR = 1.58), N (p = 0.013, RR = 2.60), and M (p < 0.001, RR = 4.14) stages and adrenal gland invasion (p = 0.001, RR = 4.91) were the most significant negative prognostic predictors.ConclusionsIn this study, we reported most cases of RCC patients with venous extension in China. We proved that patients with RCC and venous tumor thrombus may have relative promising long-term survival rate, especially those with early tumor thrombus

Isolation of cationic and neutral (allenylidene)(carbene) and bis(allenylidene)gold complexes.

The one-electron reduction of a cationic (allenylidene)[cyclic(alkyl) (amino)carbene]gold(i) complex leads to the corresponding neutral, paramagnetic, formally gold(0) complex. DFT calculations reveal that the spin density of this highly robust coinage metal complex is mainly located on the allenylidene fragment, with only 1.8 and 3.1% on the gold center and the CAAC ligand, respectively. In addition, the first homoleptic bis(allenylidene)gold(i) complex has been prepared and fully characterized

Bifurcations and Stability of Nondegenerated Homoclinic Loops for Higher Dimensional Systems

By using the foundational solutions of the linear variational equation of the unperturbed system along the homoclinic orbit as the local current coordinates system of the system in the small neighborhood of the homoclinic orbit, we discuss the bifurcation problems of nondegenerated homoclinic loops. Under the nonresonant condition, existence, uniqueness, and incoexistence of 1-homoclinic loop and 1-periodic orbit, the inexistence of k-homoclinic loop and k-periodic orbit is obtained. Under the resonant condition, we study the existence of 1-homoclinic loop, 1-periodic orbit, 2-fold 1-periodic orbit, and two 1-periodic orbits; the coexistence of 1-homoclinic loop and 1-periodic orbit. Moreover, we give the corresponding existence fields and bifurcation surfaces. At last, we study the stability of the homoclinic loop for the two cases of non-resonant and resonant, and we obtain the corresponding criterions

Contralateral upper tract urothelial carcinoma after nephroureterectomy: the predictive role of DNA methylation

Abstract Background Aberrant methylation of genes is one of the most common epigenetic modifications involved in the development of urothelial carcinoma. However, it is unknown the predictive role of methylation to contralateral new upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). We retrospectively investigated the predictive role of DNA methylation and other clinicopathological factors in the contralateral upper tract urothelial carcinoma (UTUC) recurrence after radical nephroureterectomy (RNU) in a large single-center cohort of patients. Methods In a retrospective design, methylation of 10 genes was analyzed on tumor specimens belonging to 664 consecutive patients treated by RNU for primary UTUC. Median follow-up was 48 mo (range: 3–144 mo). Gene methylation was accessed by methylation-sensitive polymerase chain reaction, and we calculated the methylation index (MI), a reflection of the extent of methylation. The log-rank test and Cox regression were used to identify the predictor of contralateral UTUC recurrence. Results Thirty (4.5%) patients developed a subsequent contralateral UTUC after a median follow-up time of 27.5 (range: 2–139) months. Promoter methylation for at least one gene promoter locus was present in 88.9% of UTUC. Fewer methylation and lower MI (P = 0.001) were seen in the tumors with contralateral UTUC recurrence than the tumors without contralateral recurrence. High MI (P = 0.007) was significantly correlated with poor cancer-specific survival. Multivariate analysis indicated that unmethylated RASSF1A (P = 0.039), lack of bladder recurrence prior to contralateral UTUC (P = 0.009), history of renal transplantation (P < 0.001), and preoperative renal insufficiency (P = 0.002) are independent risk factors for contralateral UTUC recurrence after RNU. Conclusions Our data suggest a potential role of DNA methylation in predicting contralateral UTUC recurrence after RNU. Such information could help identify patients at high risk of new contralateral UTUC recurrence after RNU who need close surveillance during follow up.http://deepblue.lib.umich.edu/bitstream/2027.42/110306/1/13046_2015_Article_120.pd

Induction of Fas mediated caspase-8 independent apoptosis in immune cells by <i>Armigeres subalbatus</i> saliva

Background It is widely recognized that the introduction of saliva of bloodsucking arthropods at the site of pathogen transmission might play a central role in vector-borne infections. However, how the interaction between salivary components and the host immune system takes place and which physiological processes this leads to has yet to be investigated. Armigeres subalbatus is one of the prominent types of mosquitoes involved in the transmission of parasitic and viral diseases in humans and animals. Methodology/Principal Findings Using murine peritoneal macrophages and lymphocytes, and human peripheral mononuclear cells (PBMCs), this study shows that saliva of the female Ar. subalbatus induces apoptosis via interaction with the Fas receptor within a few hours but without activating caspase-8. The process further activates downstream p38 MAPK signaling, a cascade that leads to the induction of apoptosis in capase-3 dependent manner. We further illustrate that Ar. subalbatus saliva suppresses proinflammatory cytokines without changing IL-10 levels, which might happen as a result of apoptosis. Conclusions Our study shows for the first time that saliva-induced apoptosis is the leading phenomenon exerted by Ar. subalbatus that impede immune cells leading to the suppression of their effecter mechanism.</br

High-Speed X-Ray Transmission and Numerical Study of Melt Flows inside the Molten Pool during Laser Welding of Aluminum Alloy

By using the X-ray transmission imaging system, melt flows inside a molten pool were studied during laser welding of aluminum alloy at different welding speeds. Then, the correlation between temperature gradients along the direction of weld penetration and melt flows in the rear part of a molten pool was analyzed by using a three-dimensional numerical method. And the presented model was verified by experimental results. The corresponding investigation was carried out to further study the correlation between temperature gradient and melt flow behavior of the molten pool in the plate heated by preheating temperature. The results indicated that, in the rear part of the molten pool, the maximum flow velocity was located at the bottom of the molten pool. The melt metal in the rear molten pool caused by different welding speeds had significantly different flow trends. As the welding speed increased, the absorbed intensity on the keyhole front wall also increased as well as the recoil pressure that could maintain the keyhole opened. Consequently, the increase of the welding speed was more beneficial to improving the stability of the molten pool

Spatiotemporal cluster patterns of hand, Foot, and mouth disease at the county level in Mainland China, 2008-2012

Background: Hand, foot, and mouth disease (HFMD) is known to be a highly contagious childhood illness. In recent years, the number of reported cases of HFMD has significantly increased in mainland China. This study aims at the epidemiological features, spatiotemporal patterns of HMFD at the county/district level in mainland China. Methods: Data on reported HFMD cases for each county from 1 January 2008 to 31 December 2012 were obtained from the Chinese Center for Disease Control and Prevention. Cluster analysis, spatial autocorrelation, and retrospective scan methods were used to explore the spatiotemporal patterns of the disease. Results: The annual incidences varied greatly among the counties, ranging from 0 to 74.31‰with the median of 5.42‰ (interquartile range: 1.54‰–13.55‰) during 2008–2012 in mainland China. Counties close to provincial capital cities generally had higher incidences than rural counties. A seasonal distribution was observed between the northern and southern China, of which dual epidemic were shown in southern China and usually only one in northern China. Based on the global and local spatial autocorrelation analysis, we found that the spatial distribution of HFMD was presented a significant clustering pattern for each year (P Conclusions: The spatiotemporal clustering areas of the disease identified in this way were relatively stable, and imminent public health planning and resource allocation should be focused within those areas