In situ loading and delivery of short single- And double-stranded dna by supramolecular organic frameworks

Short DNA represents an important class of biomacromolecules that are widely applied in gene therapy, editing, and modulation. However, the development of simple and reliable methods for their intracellular delivery remains a challenge. Herein, we describe that seven water-soluble, homogeneous supramolecular organic frameworks (SOFs) with a well-defined pore size and high stability in water that can accomplish in situ inclusion of single-stranded (ss) and double-stranded (ds) DNA (21, 23, and 58 nt) and effective intracellular delivery (including two noncancerous and six cancerous cell lines). Fluorescence quenching experiments for single and double endlabeled ss- and ds-DNA support that the DNA sequences can be completely enveloped by the SOFs. Confocal laser scanning microscopy and flow cytometry reveal that five of the SOFs exhibit excellent delivery efficiencies that, in most of the studied cases, outperform the commercial standard Lipo2000, even at low SOF-nucleic acid ratios. In addition to high delivery efficiencies, the watersoluble, self-assembled SOF carriers have a variety of advantages, including convenient preparation, high stability, and in situ DNA inclusion, which are all critical for practical applications in nucleic acid delivery

Proteome profiling of cadmium-induced apoptosis by antibody array analyses in human bronchial epithelial cells

Protein array technology is a powerful platform for the simultaneous determination of the expression levels of a number of proteins as well as post-translational modifications such as phosphorylation. Here, we screen and report for the first time, the dominant signaling cascades and apoptotic mediators during the course of cadmium (Cd)-induced cytotoxicity in human bronchial epithelial cells (BEAS-2B) by antibody array analyses. Proteins from control and Cd-treated cells were captured on Proteome Profiler™ Arrays for the parallel determination of the relative levels of protein phosphorylation and proteins associated with apoptosis. Our results indicated that the p38 MAPK- and JNK-related signal transduction pathways were dramatically activated by Cd treatment. Cd potently stimulates the phosphorylations of p38α (MAPK14), JNK1/2 (MAPK8/9), and JUN; while the phosphorylations of Akt1, ERK1/2 (MAPK3/1), GSK3β, and mTOR were suppressed. Moreover, there was an induction of proapoptotic protein BAX, release of cytochrome c (CYCS) from mitochondria, activation of caspase-3/9 (CASP3/9); as well as decreased expression of cell cycle checkpoint proteins (TP53, p21, and p27) and several inhibitors of apoptosis proteins (IAPs) [including cIAP-1/2 (BIRC2/3), XIAP (BIRC4), and survivin (BIRC5)]. Pretreatment of cells with the thiol antioxidant glutathione or p38 MAPK/JNK inhibitors before Cd treatment effectively abrogated ROS activation of p38 MAPK/JNK pathways and apoptosis-related proteins. Taken together, our results demonstrate that Cd causes oxidative stress-induced apoptosis; and the p38 MAPK/JNK and mitochondrial pathways are more importantly participated for signal transduction and the induction of apoptosis in Cd-exposed human lung cells.published_or_final_versio

Costs associated with febrile neutropenia in solid tumor and lymphoma patients - an observational study in Singapore.

BackgroundThe primary objective was to describe the total direct inpatient costs among solid tumor and lymphoma patients with chemotherapy-induced febrile neutropenia (FN) and the factors that were associated with higher direct cost. The secondary objective was to describe the out-of-pocket patient payments and the factors that were associated with higher out-of-pocket patient payments.MethodsThis was a single-center observational study conducted at the largest cancer center in Singapore. All of the adult cancer patients hospitalized due to FN from 2009 to 2012 were studied. The primary outcomes were the total hospital cost and the out-of-pocket patient payments (adjusted by government subsidy) per FN episode. Univariate analysis and multiple linear regression were conducted to identify the factors associated with higher FN costs.ResultsThree hundred and sixty seven adult cancer patients were documented with FN-related hospitalizations. The mean total hospital cost was US$4,193 (95$3,779-4,607) and the mean out-of-pocket patient payment was US$2,230 (95$1,976-2,484), per FN episode. The factors associated with a higher total hospital cost were longer length of stay, severe sepsis, and lymphoma as underlying cancer. The out-of-pocket patient payment was positively associated with longer length of stay, severe sepsis, lymphoma diagnosed as underlying cancer, the therapeutic use of granulocyte colony-stimulating factor (GCSF), the private ward class, and younger patients.ConclusionsThe total hospital cost and out-of-pocket patient payments of FN management in lymphoma cases were substantial compared with other solid tumors. Factors associated with a higher FN management cost may be useful for developing appropriate strategies to reduce the cost of FN for cancer patients

Protective effect of wild Corni fructus methanolic extract against acute alcoholic liver injury in mice

Background: In Chinese folk medicine, Corni fructus (C. fructus) has traditionally been used to improve liver function, although the mechanism underlying its activity remains unclear. The aim of the present study was to evaluate the protective effects of wild C. fructus methanolic extract against acute alcoholic liver injury.Methods: Alcohol was administered to mice for three consecutive days, either alone or in combination with C. fructus methanolic extract (50, 100, or 200mg/kg body weight/d). Serum and liver tissue were collected from the animals and subjected to biochemical and histopathological analyses.Results:C. fructus significantly alleviated alcohol-induced liver injury by reducing serum alanine aminotransferase, aspartate aminotransferase, and thiobarbituric acid reactive species, inhibiting hydroxyl radicals (center dot OH), and increasing total superoxide dismutase, glutathione peroxidase, and glutathione in the liver (P<0.05). In addition, the C. fructus treatment inhibited the expression and activity of cytochrome P450 2E1 (P<0.05)Conclusions:C. fructus could be a promising natural substance for ameliorating acute alcohol-induced oxidative stress and hepatic injury.- This work was supported by the Construction Project of Shaanxi Collaborative Innovation Center (2015, Shaanxi Sci-tech University); High-End Foreign Experts Recruitment Program [Grant GDW20146100228]; and Key Construction Program of International Cooperation Base in S&T Shaanxi Province, China [Grant 2015SD0018].info:eu-repo/semantics/publishedVersio

Inexact fuzzy-stochastic constraint-softened programming - A case study for waste management

In this study, an inexact fuzzy-stochastic constraint-softened programming method is developed for municipal solid waste (MSW) management under uncertainty, The developed method can deal with multiple uncertainties presented in terms of fuzzy sets, interval values and random variables. Moreover, a number of violation levels for the system constraints are allowed. This is realized through introduction of violation variables to soften system constraints, such that the model's decision space can be expanded under demanding conditions. This can help generate a range of decision alternatives under various conditions, allowing in-depth analyses of tradeoffs among economic objective, satisfaction degree, and constraint-violation risk. The developed method is applied to a case study of planning a MSW management system. The uncertain and dynamic information can be incorporated within a multi-layer scenario tree; revised decisions are permitted in each time period based on the realized values of uncertain events. Solutions associated with different satisfaction degree levels have been generated, corresponding to different constraint-violation risks. They are useful for supporting decisions of waste flow allocation and system-capacity expansion within a multistage context. (C) 2008 Elsevier Ltd. All rights reserved

Use of moxibustion to treat primary dysmenorrhea at two interventional times: study protocol for a randomized controlled trial

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The disposition and pharmacokinetics of Dioscorea nipponica Makino extract in rats

This study was aimed to investigate the disposition and pharmacokinetics of the total saponins of dioscorea (TSD) in rats. Male Sprague-Dawley rats were orally administrated with 3H labeled TSD at a single dose ratio of 80 mg TSD per 1 kg rat. Blood samples and feces were collected at different time points to measure the level of TSD activity. At the final time point, determination of the disposition of TSD in lung, kidney, heart, liver, adrenal, and small intestine were performed. From the blood samples' emission of radioactivity, pharmacokinetic parameters were derived as T1/2 = 33.33 ± 4.48 h, T max = 6.5 ± 0.71 h, AUC = 119400 ± 421097.67, and C max = 2643.33 ± 192.26 dpm/ml. There was 51.609% of 3H labeled substance excreted in 24 h. These results suggested that blood concentration of 3H-TSD was extremely low and the majority of TSD was excreted in the feces. The TSD was extensively distributed to multitissues. The radioactivity level was measured to be the highest in the liver, adrenal gland, and wall of the gastrointestinal tract. The radioactivity of TSD was still being detected in blood after 96 h. This showed TSD was excreted in vivo very slowly. © 2008 Academic Journals.published_or_final_versio

From regional pulse vaccination to global disease eradication: insights from a mathematical model of Poliomyelitis

Mass-vaccination campaigns are an important strategy in the global fight against poliomyelitis and measles. The large-scale logistics required for these mass immunisation campaigns magnifies the need for research into the effectiveness and optimal deployment of pulse vaccination. In order to better understand this control strategy, we propose a mathematical model accounting for the disease dynamics in connected regions, incorporating seasonality, environmental reservoirs and independent periodic pulse vaccination schedules in each region. The effective reproduction number, $R_e$, is defined and proved to be a global threshold for persistence of the disease. Analytical and numerical calculations show the importance of synchronising the pulse vaccinations in connected regions and the timing of the pulses with respect to the pathogen circulation seasonality. Our results indicate that it may be crucial for mass-vaccination programs, such as national immunisation days, to be synchronised across different regions. In addition, simulations show that a migration imbalance can increase $R_e$ and alter how pulse vaccination should be optimally distributed among the patches, similar to results found with constant-rate vaccination. Furthermore, contrary to the case of constant-rate vaccination, the fraction of environmental transmission affects the value of $R_e$ when pulse vaccination is present.Comment: Added section 6.1, made other revisions, changed titl

Spatio-Temporal Characteristics of Global Warming in the Tibetan Plateau during the Last 50 Years Based on a Generalised Temperature Zone - Elevation Model

Temperature is one of the primary factors influencing the climate and ecosystem, and examining its change and fluctuation could elucidate the formation of novel climate patterns and trends. In this study, we constructed a generalised temperature zone elevation model (GTEM) to assess the trends of climate change and temporal-spatial differences in the Tibetan Plateau (TP) using the annual and monthly mean temperatures from 1961-2010 at 144 meteorological stations in and near the TP. The results showed the following: (1) The TP has undergone robust warming over the study period, and the warming rate was 0.318°C/decade. The warming has accelerated during recent decades, especially in the last 20 years, and the warming has been most significant in the winter months, followed by the spring, autumn and summer seasons. (2) Spatially, the zones that became significantly smaller were the temperature zones of -6°C and -4°C, and these have decreased 499.44 and 454.26 thousand sq km from 1961 to 2010 at average rates of 25.1% and 11.7%, respectively, over every 5-year interval. These quickly shrinking zones were located in the northwestern and central TP. (3) The elevation dependency of climate warming existed in the TP during 1961-2010, but this tendency has gradually been weakening due to more rapid warming at lower elevations than in the middle and upper elevations of the TP during 1991-2010. The higher regions and some low altitude valleys of the TP were the most significantly warming regions under the same categorizing criteria. Experimental evidence shows that the GTEM is an effective method to analyse climate changes in high altitude mountainous regions

Spin and valley quantum Hall ferromagnetism in graphene

In a graphene Landau level (LL), strong Coulomb interactions and the fourfold spin/valley degeneracy lead to an approximate SU(4) isospin symmetry. At partial filling, exchange interactions can spontaneously break this symmetry, manifesting as additional integer quantum Hall plateaus outside the normal sequence. Here we report the observation of a large number of these quantum Hall isospin ferromagnetic (QHIFM) states, which we classify according to their real spin structure using temperature-dependent tilted field magnetotransport. The large measured activation gaps confirm the Coulomb origin of the broken symmetry states, but the order is strongly dependent on LL index. In the high energy LLs, the Zeeman effect is the dominant aligning field, leading to real spin ferromagnets with Skyrmionic excitations at half filling, whereas in the `relativistic' zero energy LL, lattice scale anisotropies drive the system to a spin unpolarized state, likely a charge- or spin-density wave.Comment: Supplementary information available at http://pico.phys.columbia.ed