Low-Frequency Repetitive Transcranial Magnetic Stimulation Ameliorates Cognitive Function and Synaptic Plasticity in APP23/PS45 Mouse Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is a chronic neurodegenerative disease leading to dementia, which is characterized by progressive memory loss and other cognitive dysfunctions. Recent studies have attested that noninvasive repetitive transcranial magnetic stimulation (rTMS) may help improve cognitive function in patients with AD. However, the majority of these studies have focused on the effects of high-frequency rTMS on cognitive function, and little is known about low-frequency rTMS in AD treatment. Furthermore, the potential mechanisms of rTMS on the improvement of learning and memory also remain poorly understood. In the present study, we reported that severe deficits in spatial learning and memory were observed in APP23/PS45 double transgenic mice, a well known mouse model of AD. Furthermore, these behavioral changes were accompanied by the impairment of long-term potentiation (LTP) in the CA1 region of hippocampus, a brain region vital to spatial learning and memory. More importantly, 2-week low-frequency rTMS treatment markedly reversed the impairment of spatial learning and memory as well as hippocampal CA1 LTP. In addition, low-frequency rTMS dramatically reduced amyloid-β precursor protein (APP) and its C-terminal fragments (CTFs) including C99 and C89, as well as β-site APP-cleaving enzyme 1 (BACE1) in the hippocampus. These results indicate that low-frequency rTMS noninvasively and effectively ameliorates cognitive and synaptic functions in a mouse model of AD, and the potential mechanisms may be attributed to rTMS-induced reduction in Aβ neuropathology

Association Analysis and Identification of ZmHKT1;5 Variation With Salt-Stress Tolerance

The high-affinity potassium transporter (HKT) genes are essential for plant salt stress tolerance. However, there were limited studies on HKTs in maize (Zea mays), and it is basically unknown whether natural sequence variations in these genes are associated with the phenotypic variability of salt tolerance. Here, the characterization of ZmHKT1;5 was reported. Under salt stress, ZmHKT1;5 expression increased strongly in salt-tolerant inbred lines, which accompanied a better-balanced Na+/K+ ratio and preferable plant growth. The association between sequence variations in ZmHKT1;5 and salt tolerance was evaluated in a diverse population comprising 54 maize varieties from different maize production regions of China. Two SNPs (A134G and A511G) in the coding region of ZmHKT1;5 were significantly associated with different salt tolerance levels in maize varieties. In addition, the favorable allele of ZmHKT1; 5 identified in salt tolerant maize varieties effectively endowed plant salt tolerance. Transgenic tobacco plants of overexpressing the favorable allele displayed enhanced tolerance to salt stress better than overexpressing the wild type ZmHKT1;5. Our research showed that ZmHKT1;5 expression could effectively enhance salt tolerance by maintaining an optimal Na+/K+ balance and increasing the antioxidant activity that keeps reactive oxygen species (ROS) at a low accumulation level. Especially, the two SNPs in ZmHKT1;5 might be related with new amino acid residues to confer salt tolerance in maize.Key Message: Two SNPs of ZmHKT1;5 related with salt tolerance were identified by association analysis. Overexpressing ZmHKT1;5 in tobaccos showed that the SNPs might enhance its ability to regulating Na+/K+ homeostasis

Active learning with label quality control

Training deep neural networks requires a large number of labeled samples, which are typically provided by crowdsourced workers or professionals at a high cost. To obtain qualified labels, samples need to be relabeled for inspection to control the quality of the labels, which further increases the cost. Active learning methods aim to select the most valuable samples for labeling to reduce labeling costs. We designed a practical active learning method that adaptively allocates labeling resources to the most valuable unlabeled samples and the most likely mislabeled labeled samples, thus significantly reducing the overall labeling cost. We prove that the probability of our proposed method labeling more than one sample from any redundant sample set in the same batch is less than 1/k, where k is the number of the k-fold experiment used in the method, thus significantly reducing the labeling resources wasted on redundant samples. Our proposed method achieves the best level of results on benchmark datasets, and it performs well in an industrial application of automatic optical inspection

Idraparinux or idrabiotaparinux for long-term venous thromboembolism treatment: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Venous thromboembolism (VTE) is a prevalent disease with potential serious consequences. Idraparinux and idrabiotaparinux are two kinds of long-acting pentasaccharides. Evidence has shown that idraparinux and idrabiotaparinux are effective anticoagulants. However, up to now, there is no consensus on whether they are better than other anticoagulation methods for long-term VTE treatment. OBJECTIVE: To evaluate the effect of idraparinux or idrabiotaparinux versus other anticoagulation methods for long-term VTE treatment. METHODS: We searched Cochrane Central Register of Controlled Trials, PubMed, Embase, Web of science, clinical trial registry web sites (clinical trials,WHO clinical trial registry), Googlescholar, PubMed related articles and companies' web sites electronically up to Dec 30(th), 2012 and manually searched the reference lists and conference proceedings. Only randomized controlled trial (RCT) involving adult patients comparing idraparinux and/or idrabiotaparinux versus other anticoagulation methods for long-term VTE treatment was included. Two reviewers evaluated the studies and extracted data independently. Pooled risk ratios (RRs) were calculated as outcome measures and Revman 5.2 software was used to analyze data. Our primary efficacy and safety outcomes were the recurrent VTE and major bleeding rates. RESULTS: We included four RCTs and involved 8584 participants on idraparinux or idrabiotaparinux versus standard warfarin for VTE treatment from 9364 references. We did not perform meta-analysis on the VTE rate because of the significant heterogeneity. We used the fixed effect model to analyze the safety outcomes and demonstrated that idraparinux or idrabiotaparinux decreased major bleeding rate significantly (RR 0.73, 95% CI 0.54 to 0.98, P = 0.04) but had a trend to increase the all cause mortality (RR 1.26, 95% CI 1.00 to 1.57, P = 0.05) compared with warfarin. CONCLUSIONS: Until now there is not sufficient evidence to clarify whether idraparinux or idrabiotaparinux is as effective and safe as the standard warfarin treatment for VTE treatment

A Portable Biosensor Based on Au Nanoflower Interface Combined with Electrochemical Immunochromatography for POC Detection of Prostate-Specific Antigen

Serum prostate-specific antigen (PSA) is a widely used for the detection of prostate cancer and is considered the most reliable biomarker. However, the currently reported detection methods cannot achieve rapid monitoring. Here, we report a novel electrochemical immunochromatography (EIC) system for clinically accurate PSA detection. First, we constructed a carbon interface modified with gold nanoflowers (Au NFs) based on screen-printed carbon electrodes (SPCE), which acted as nanostructures with larger specific surface area that increased the number of PSA capture antibodies and can further improve detection signal-to-noise (S/N) ratio. Then, we fabricated detection chips by combining the SPCE/Au NFs with EIC. Under optimized conditions, the proposed biosensor exhibits high accuracy, taking only 15 minutes to complete detection. By measuring the levels of PSA in clinical blood samples, the biosensor can successfully discriminate clinically diagnosed prostate cancer patients from healthy controls

Electrochemical Biosensing Methods for Detecting Epigenetic Modifications

Epigenetic modifications are closely related to diseases and physiological health, mainly including DNA methylation, RNA methylation, histone acetylation, and noncoding RNA. Recently, a large amount of research has been conducted on the detection of epigenetic modifications. Electrochemical biosensors, with their low cost, high sensitivity, high compatibility, and simple operation, have been widely used in the detection of epigenetic biomarkers. This review discusses the detection of epigenetic biomarkers using different electrochemical sensing methods. Here we discuss various aspects, including free labels, signal labeling, signal amplification, nano-based electrodes, and the combined use of other methods. By summarizing the existing electrochemical detection methods for epigenetic modifications, this review also proposes future development trends and challenges for electrochemical biosensors in this field

Quality assessment of included studies.

<p>DVT deep venous thrombosis; PE, pulmonary embolism. Supporting Information Legends.</p