High-Definition DNA Methylation Profiles from Breast and Ovarian Carcinoma Cell Lines with Differing Doxorubicin Resistance

Acquired drug resistance represents a frequent obstacle which hampers efficient chemotherapy of cancers. The contribution of aberrant DNA methylation to the development of drug resistant tumor cells has gained increasing attention over the past decades. Hence, the objective of the presented study was to characterize DNA methylation changes which arise from treatment of tumor cells with the chemotherapeutic drug doxorubicin. DNA methylation levels from CpG islands (CGIs) linked to twenty-eight genes, whose expression levels had previously been shown to contribute to resistance against DNA double strand break inducing drugs or tumor progression in different cancer types were analyzed. High-definition DNA methylation profiles which consisted of methylation levels from 800 CpG sites mapping to CGIs around the transcription start sites of the selected genes were determined. In order to investigate the influence of CGI methylation on the expression of associated genes, their mRNA levels were investigated via qRT-PCR. It was shown that the employed method is suitable for providing highly accurate methylation profiles, comparable to those obtained via clone sequencing, the gold standard for high-definition DNA methylation studies. In breast carcinoma cells with acquired resistance against the double strand break inducing drug doxorubicin, changes in methylation of specific cytosines from CGIs linked to thirteen genes were detected. Moreover, similarities between methylation profiles obtained from breast and ovarian carcinoma cell lines with acquired doxorubicin resistance were found. The expression levels of a subset of analyzed genes were shown to be linked to the methylation levels of the analyzed CGIs. Our results provide detailed DNA methylation information from two separate model systems for acquired doxorubicin resistance and suggest the occurrence of similar methylation changes in both systems upon exposure to the drug

Estimation of HIV-1 incidence among five focal populations in Dehong, Yunnan: a hard hit area along a major drug trafficking route

<p>Abstract</p> <p>Background</p> <p>Since 1989 when the first 146 HIV positives in China were identified, Dehong Prefecture had been one of the areas hardest-hit by HIV in China. The local and national governments have put substantial financial resources into tackling the HIV epidemic in Dehong from 2004. The objective of this study was to track dynamic changes in HIV-1 prevalence and incidence among five focal populations in Dehong and to assess the impact of HIV prevention and control efforts.</p> <p>Methods</p> <p>Consecutive cross-sectional surveys conducted in five focal populations between 2004 and 2008. Specimens seropositive for HIV were tested with the BED IgG capture enzyme immunoassay to identify recent seroconversions (median, 155 days) using normalized optical density of 0.8 and adjustments.</p> <p>Results</p> <p>From 2004 to 2008, estimated annual HIV incidence among injecting drug users (IDUs) decreased significantly [from 15.0% (95% CI = 11.4%-18.5%) in 2004 to 4.3% (95% CI = 2.4%-6.2%) in 2008; trend test P < 0.0001]. The incidence among other focal populations, such as HIV discordant couples (varying from 5.5% to 4.7%), female sex workers (varying from 1.4% to 1.3%), pregnant women (0.1%), and pre-marital couples (0.2 to 0.1%) remained stable. Overall, the proportion of recent HIV-1 infections was higher among females than males (P < 0.0001).</p> <p>Conclusions</p> <p>The HIV epidemic in Dehong continued to expand during a five-year period but at a slowing rate among IDUs, and HIV incidence remains high among IDUs and discordant couples. Intensive prevention measures should target sub-groups at highest risk to further slow the epidemic and control the migration of HIV to other areas of China, and multivariate analysis is needed to explore which measures are more effective for different populations.</p

Monitoring Wireless Sensor Networks by Heterogeneous Collaborative Groupware

Abstract – This paper presents a pioneer work on using heterogeneous collaborative groupware to monitor wireless sensor networks. The prototype implementation illustrates that wireless sensor networks can be integrated into a larger scale, heterogeneous, collaborative groupware to enable complicated and/or geographically unbounded applications that require inputs from sensors, intelligent agents, and human participants. I

Bioactivity-Guided Separation of Anti-Cholinesterase Alkaloids from Uncaria rhynchophlly (Miq.) Miq. Ex Havil Based on HSCCC Coupled with Molecular Docking

As an important source of cholinesterase inhibitors, alkaloids in natural products have high potential value in terms of exerting pharmacological activities. In this study, a strategy for targeted preparation of cholinesterase inhibitors in Uncaria rhynchophlly (Miq.) Miq. ex Havil (UR) by high-speed counter-current chromatography was provided. In the method, a two-phase polar solvent system composed of ethyl acetate/n-butanol/water (1:4:5, v/v/v) was used, which isolated five alkaloids from the UR extract for the first time. All alkaloids were identified by HR-ESI-MS and NMR as 7-epi-javaniside (1), vincosamide (2), strictosamide (3), cadambine (4), and 3&alpha;-dihydrocadambine (5). The poorly resolved compounds 2 and 3 were separated by preparative HPLC (prep-HPLC). Among them, compounds 1, 4, and 5 were firstly obtained from UR. The purity of these plant isolates was 98.8%, 98.7%, 99.2%, 95.7%, and 98.5%, respectively. Compounds 1&ndash;5 exhibited an inhibitory effect on acetyl-cholinesterase and butyryl-cholinesterase with an IC50 from 1.47 to 23.24 &micro;g/mL and 1.01 to 18.24 &micro;g/mL. Molecular docking and inhibitory activities indicated that compound 1 showed stronger inhibitory activity on acetyl-cholinesterase and butyryl-cholinesterase

Selective Electrochemical Reduction of CO₂ to Ethylene on Nanopores-Modified Copper Electrodes in Aqueous Solution

Electrochemical reduction of carbon dioxide was carried out on copper foil electrodes modified with nanopores on the surface. Such nanopores modified structure was obtained through an alloying–dealloying process. Scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy confirmed the formation of alloy layer and the final nanoporous morphology of such copper electrodes. When used in electrolysis process, the as-prepared nanopores-modified electrodes can suppress the Faradaic efficiency toward methane to less than 1%, while keeping that of ethylene in a high level of 35% in aqueous 0.1 M KHCO₃ solution under −1.3 V (vs reversible hydrogen electrode), thus revealing a remarkable selectivity toward ethylene production. The high yield of ethylene can be ascribed to the exposed specific crystalline orientations

Smart MXene‐based bioelectronic devices as wearable health monitor for sensing human physiological signals

Abstract Biosafe wearable healthcare monitor has attracted significant attention owing to their applicability to wearable electronics. However, the narrow sensing range and poor response limit the application of flexible devices for comprehensive monitoring of human health‐related physiological signals (i.e., pulse diagnosis). Critical challenges remain in the development of biocompatible materials and the design of flexible bio‐integrated platforms for these purposes, targeting performance approaching those of conventional wafer‐based technologies and long‐term operational stability. In this context, this work presents a robust and flexible MXene/polydopamine (PDA)‐composite‐film‐based pressure sensor in a portable/wearable fashion, which establishes a unique intercalated spherical‐like PDA molecules structure, thereby resulting in excellent sensing performance. The MXene/PDA‐based pressure sensor has sensitivity of up to 138.8 kPa−1 in the pressure range of 0.18–6.20 kPa with fast response and recovery speed (t1 < 100 ms; t2< 50 ms). Associated embodiment involves real‐time precise measurements of a variety of health‐related physiological signals, ranging from wrist pulse, to finger motions, to vocalization and to facial expressions, with high sensitivity and accuracy. Studies on human subjects establish the clinical significance of these devices for future opportunities of health monitoring and intelligent control to predict and diagnose diseases

Estimates of HIV prevalence in a highly endemic area of China: Dehong Prefecture, Yunnan Province

Background Dehong Prefecture in Yunnan Province, China, borders Myanmar. Its proximity to the ‘Golden Triangle’, one of the world's largest illicit drug production and distribution centre, contributes to drug trafficking and ready availability of heroin. Dehong's 1.1 million people confront a serious HIV problem fuelled by injection drug use. The aim of this study is to improve the 2005 estimates of the true status of the HIV/AIDS epidemic in Dehong Prefecture