Minocycline inhibits hyperpolarization-activated currents in rat substantia gelatinosa neurons

AbstractMinocycline is a widely used glial activation inhibitor that could suppress pain-related behaviors in a number of different pain animal models, yet, its analgesic mechanisms are not fully understood. Hyperpolarization-activated cation channel-induced Ih current plays an important role in neuronal excitability and pathological pain.In this study, we investigated the possible effect of minocycline on Ih of substantia gelatinosa neuron in superficial spinal dorsal horn by using whole-cell patch-clamp recording.We found that extracellular minocycline rapidly decreases Ih amplitude in a reversible and concentration-dependent manner (IC50 = 41 μM). By contrast, intracellular minocycline had no effect. Minocycline-induced inhibition of Ih was not affected by Na+ channel blocker tetrodotoxin, glutamate-receptor antagonists (CNQX and D-APV), GABAA receptor antagonist (bicuculine methiodide), or glycine receptor antagonist (strychnine). Minocycline also caused a negative shift in the activation curve of Ih, but did not alter the reversal potential. Moreover, minocycline slowed down the inter-spike depolarizing slope and produced a robust decrease in the rate of action potential firing.Together, these results illustrate a novel cellular mechanism underlying minocycline's analgesic effect by inhibiting Ih currents of spinal dorsal horn neurons

DeViT: Decomposing Vision Transformers for Collaborative Inference in Edge Devices

Recent years have witnessed the great success of vision transformer (ViT), which has achieved state-of-the-art performance on multiple computer vision benchmarks. However, ViT models suffer from vast amounts of parameters and high computation cost, leading to difficult deployment on resource-constrained edge devices. Existing solutions mostly compress ViT models to a compact model but still cannot achieve real-time inference. To tackle this issue, we propose to explore the divisibility of transformer structure, and decompose the large ViT into multiple small models for collaborative inference at edge devices. Our objective is to achieve fast and energy-efficient collaborative inference while maintaining comparable accuracy compared with large ViTs. To this end, we first propose a collaborative inference framework termed DeViT to facilitate edge deployment by decomposing large ViTs. Subsequently, we design a decomposition-and-ensemble algorithm based on knowledge distillation, termed DEKD, to fuse multiple small decomposed models while dramatically reducing communication overheads, and handle heterogeneous models by developing a feature matching module to promote the imitations of decomposed models from the large ViT. Extensive experiments for three representative ViT backbones on four widely-used datasets demonstrate our method achieves efficient collaborative inference for ViTs and outperforms existing lightweight ViTs, striking a good trade-off between efficiency and accuracy. For example, our DeViTs improves end-to-end latency by 2.89$\times$ with only 1.65% accuracy sacrifice using CIFAR-100 compared to the large ViT, ViT-L/16, on the GPU server. DeDeiTs surpasses the recent efficient ViT, MobileViT-S, by 3.54% in accuracy on ImageNet-1K, while running 1.72$\times$ faster and requiring 55.28% lower energy consumption on the edge device.Comment: Accepted by IEEE Transactions on Mobile Computin

Increased Expression and Altered Methylation of HERVWE1 in the Human Placentas of Smaller Fetuses from Monozygotic, Dichorionic, Discordant Twins

<div><h3>Background</h3><p>The human endogenous retroviral family W, Env(C7), member 1 gene (<em>HERVWE1</em>) is thought to participate in trophoblast cell fusion, and its expression is diminished in the placentas of singleton intrauterine growth-retarded pregnancies. However, there is limited information about the role of <em>HERVWE1</em> in discordant fetal growth in twins. This study was to compare <em>HERVWE1</em> gene expression between the placentas of discordant monozygotic twins and to identify its regulation by methylation.</p> <h3>Methodology/Principal Findings</h3><p>Fetuses from twenty-one pairs of monozygotic, dichorionic, discordant twins were marked as “smaller” or “larger” according to birth weight. Placental <em>HERVWE1</em> mRNA and protein expression profiles were analyzed using quantitative RT-PCR and immunohistochemistry (IHC) staining. Methylation profiles of the <em>HERVWE1</em> promoter region were analyzed using a pyrosequencing assay. DNA methyltransferase (<em>DNMT</em>) transcript levels were analyzed by RT-PCR. 5-methyl cytosine (5-MC) was stained using an immunohistochemical assay. There was a significant negative correlation between <em>HERVWE1</em> mRNA levels and birth weight in twins (<em>P</em><0.01). Whereas the mean methylation level of the <em>HERVWE1</em> promoter region was diminished in the smaller group in discordant twins(<em>P</em><0.01), increased mRNA and protein levels of <em>HERVWE1</em> were found in smaller fetuses compared with larger fetuses in discordant twins(<em>P</em><0.01). There was no significant difference in 5-MC staining intensity between discordant twins (<em>P</em>>0.05). The <em>DNMT3b3</em> mRNA levels in the smaller group were significantly downregulated compared with the larger group in discordant twins(<em>P</em><0.05), whereas the <em>DNMT3b7</em> mRNA levels in the smaller group were significantly upregulated compared with the larger group in discordant twins(<em>P</em><0.05).</p> <h3>Conclusions/Significance</h3><p>In discordant, monozygotic, dichorionic twins, <em>HERVWE1</em> expression was higher in smaller fetuses and lower in larger fetuses. Methylation of the <em>HERVWE1</em> gene promoter region may participate in the regulation of <em>HERVWE1</em> gene expression in discordant twin pregnancies.</p> </div

Job seekers’acceptance towards producing video resumes for company’s recruitment

The purpose of this study is to explore the job seekers’ acceptance towards producing video resumes for the company’s video-based recruitment. The study aims to analyse the moderating effect of self-video resumes by experienced and non-experienced applicants’ in terms of their perceived stress and coping strategies in creating the videos when applying for jobs. The quota sampling method was used to collect data from four faculties in a private university. The conceptual model was developed with constructs consisting of perceived stress, problem-focused coping, self-efficacy, self presentation and acceptance of video resumes. The model was validated by two-level confirmatory factor analysis (CFA). Subsequently, the moderation effects between the two groups of applicants were computed to uncover different group behaviors. The perceived stress and problem-focused coping responses were found to be significantly related to self-presentations for video resumes. A direct positive relationship was also found between the applicants’ self-efficacy and their acceptance of video resumes. The results of the moderation analysis indicate a significant difference in perceived stress between groups but not in the problem-focused coping strategies

Mutant p53 Gains Its Function via c-Myc Activation upon CDK4 Phosphorylation at Serine 249 and Consequent PIN1 Binding

TP53 missense mutations significantly influence the development and progression of various human cancers via their gain of new functions (GOF) through different mechanisms. Here we report a unique mechanism underlying the GOF of p53-R249S (p53-RS), a p53 mutant frequently detected in human hepatocellular carcinoma (HCC) that is highly related to hepatitis B infection and aflatoxin B1. A CDK inhibitor blocks p53-RS\u2019s nuclear translocation in HCC, whereas CDK4 interacts with p53-RS in the G1/S phase of the cells, phosphorylates it, and enhances its nuclear localization. This is coupled with binding of a peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) to p53-RS, but not the p53 form with mutations of four serines/threonines previously shown to be crucial for PIN1 binding. As a result, p53-RS interacts with c-Myc and enhances c-Myc-dependent rDNA transcription key for ribosomal biogenesis. These results unveil a CDK4-PIN1-p53-RS-c-Myc pathway as a novel mechanism for the GOF of p53-RS in HCC

Non-invasive evaluation of ventricular refractoriness and its dispersion during ventricular fibrillation in patients with implantable cardioverter defibrillator

BACKGROUND: Local ventricular refractoriness and its dispersion during ventricular fibrillation (VF) have not been well evaluated, due to methodological difficulties. METHODS: In this study, a non-invasive method was used in evaluation of local ventricular refractoriness and its dispersion during induced VF in 11 patients with VF and/or polymorphic ventricular tachycardia (VT) who have implanted an implantable cardioverter defibrillator (ICD). Bipolar electrograms were simultaneously recorded from the lower oesophagus behind the posterior left ventricle (LV) via an oesophageal electrode and from the right ventricular (RV) apex via telemetry from the implanted ICD. VF intervals were used as an estimate of the ventricular effective refractory period (VERP). In 6 patients, VERP was also measured during sinus rhythm at the RV apex and outflow tract (RVOT) using conventional extra stimulus technique. RESULTS: Electrograms recorded from the RV apex and the lower esophagus behind the posterior LV manifested distinct differences of the local ventricular activities. The estimated VERPs during induced VF in the RV apex were significantly shorter than that measured during sinus rhythm using extra stimulus technique. The maximal dispersion of the estimated VERPs during induced VF between the RV apex and posterior LV was that of 10 percentile VF interval (40 ± 27 ms), that is markedly greater than the previously reported dispersion of ventricular repolarization without malignant ventricular arrhythmias (30–36 ms). CONCLUSIONS: This study verified the feasibility of recording local ventricular activities via oesophageal electrode and via telemetry from an implanted ICD and the usefulness of VF intervals obtained using this non-invasive technique in evaluation of the dispersion of refractoriness in patients with ICD implantation

Human Streptococcus suis Outbreak, Sichuan, China

Streptococcus suis outbreak was associated with exposure to sick or dead pigs