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Nerve injury-induced alternations of gene expression in primary sensory neurons of the dorsal root ganglion (DRG) are molecular basis of neuropathic pain genesis. Transcription factors regulate gene expression. In this study, we examined whether early B cell factor 1 (EBF1), a transcription factor, in the DRG, participated in neuropathic pain caused by chronic constriction injury (CCI) of the sciatic nerve. EBF1 was distributed exclusively in the neuronal nucleus and coexpressed with cytoplasmic/membrane Kv1.2 in individual DRG neurons. The expression of Ebf1 mRNA and protein was time-dependently downregulated in the ipsilateral lumbar (L) 3/4 DRGs after unilateral CCI. Rescuing this downregulation through microinjection of the adeno-associated virus 5 expressing full-length Ebf1 mRNA into the ipsilateral L3/4 DRGs reversed the CCI-induced decrease of DRG Kv1.2 expression and alleviated the development and maintenance of mechanical, heat and cold hypersensitivities. Conversely, mimicking the downregulation of DRG EBF1 through microinjection of AAV5-expressing Ebf1 shRNA into unilateral L3/4 DRGs produced a reduction of Kv1.2 expression in the ipsilateral L3/4 DRGs, spontaneous pain, and the enhanced responses to mechanical, heat and cold stimuli in naive mice. Mechanistically, EBF1 not only bound to the Kcna2 gene (encoding Kv1.2) promoter but also directly activated its activity. CCI decreased the EBF1 binding to the Kcna2 promoter in the ipsilateral L3/4 DRGs. Our findings suggest that DRG EBF1 downregulation contributes to neuropathic pain likely by losing its binding to Kcna2 promoter and subsequently silencing Kv1.2 expression in primary sensory neurons. Exogenous EBF1 administration may mitigate neuropathic pain by rescuing DRG Kv1.2 expression. [ABSTRACT FROM AUTHOR]

Purpose To retrospectively evaluate the effectiveness and safety of CT-guided 125 I seed brachytherapy (CTISB) in 38 non–small cell lung cancer (NSCLC) patients with locoregional recurrence (LRR). Methods and Materials In total, we analyzed 38 NSCLC patients with LRR treated with percutaneous CTISB in our hospital between 2001 and 2008; among them, 15 also received combined chemotherapy: 1–6 cycles (median, 2) of platinum-based regimens. The change in tumor volume was evaluated based on followup contrast material-enhanced CT or positron emission tomography scans. Results The median Day 0 dosimetry was as follows: The volume treated with the prescription dose ( V 100 ) was 96.3% (90.1–123.5%), and the minimum dose received by at least 90% of the tumor volume ( D 90 ) was 124.8 Gy (116.0–130.7 Gy). The median duration of the followup period calculated from the first CTISB treatment was 22.5 months (range, 8–98 months). Two months after CTISB, complete response, partial response, and progressive disease were observed in 50%, 37%, and 8% of patients, respectively. Median overall survival (OS) after CTISB was 21 months (95% confidence interval, 7.4–34.6), and the rates of 2-year OS, progression-free survival, and local control were 47.4%, 39.5%, and 83.5%, respectively. Both univariate and multivariate analysis indicated that D 90 was significant prognostic factors for OS and progression-free survival. Conclusion For selected NSCLC patients with limited LRR, CTISB is effective and can provide a high rate of local cancer control with minimal trauma. [ABSTRACT FROM AUTHOR]

Magnetorheological gel (MRG) excels in the material properties in term of adjustability and sedimentation performance, which could upgrade the performances of the current magnetorheological fluid based adjustable devices for structural control and vibration mitigation. However, the characterization and modelling of the stress-strain hysteresis responses of MRG has not been reported in the past, which are fundamental steps towards engineering applications. In this study, the stress-strain hysteresis of polyurethane based MRG sample with 60% carbonyl iron particle weight fraction was characterized under sinusoidal shear excitations with broad ranges of strain amplitude (5%–100%), excitation frequency (0.1 Hz–2 Hz) and magnetic fields (0–0.91 T). Significant stress overshooting phenomenon were observed under the application of low magnetic fields (0.27 T). A structurally-simple and accurate phenomenological model has been established to capture this unique nonlinearity. By validating the experimental results, the proposed model accurately predicts the hysteretic behaviour and the overshoot of the MRG under the excitation scenarios and the magnetic fields considered. Finally, the support vector machine (SVM) was implemented to provide the solution to the model generalization. The SVM-assisted model showed good agreement with the experimental data and can benefit the efficiency and viability in developing controllable MRG-based devices and system. Unlabelled Image • Comprehensive experimental characterization of the stress-strain hysteresis relationship of magnetorheological gel. • Discovered the stress overshoot behaviour in magnetorheological gel upon on the application of low level magnetic field. • Establishment of a four-parameter overshoot model to portray the nonlinear behaviour of magnetorheological gel. • Generalization of the four-parameter overshoot model by support vector machine method. [ABSTRACT FROM AUTHOR]

• 2% H 2 protects against sepsis-induced cognitive impairment in septic mice. • 2% H 2 decreases DNMT1, DNMT3a but not DNMT3b levels in the hippocampus. • 2% H 2 enhances BDNF levels through hypomethylating the BDNF promoter IV. Sepsis-associated encephalopathy (SAE) can cause acute and long-term cognitive impairment and increase the mortality rate in sepsis patients, and we previously reported that 2% hydrogen gas (H 2) inhalation has a therapeutic effect on SAE, but the underlying mechanism remains unclear. Dynamic DNA methylation, which catalyzed by DNA methyltransferases (DNMTs), is involved in the formation of synaptic plasticity and cognitive memory in the central nervous system. And brain-derived neurotrophic factor (BDNF), to be a key signaling component in activity-dependent synaptic plasticity, can be induced by neuronal activity accompanied by hypomethylation of its promoter IV. This study was designed to illustrate whether H 2 can mediate SAE by alter the BDNF promoter IV methylation mediated by DNMTs. We established an SAE model by cecal ligation and perforation (CLP) in C57BL/6 mice. The Morris water maze test from the 4th to the 10th day after sham or CLP operations were used to evaluate mouse cognitive function. Hippocampal tissues were isolated at the 24 after sham or CLP surgery. Pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6) and High Mobility Group Box 1 (HMGB1) were measured by enzyme-linked immunosorbent assay (ELISA). mRNA or protein levels of DNMTs (DNMT1, DNMT3a and DNMT3b), BDNF promoter IV and total BDNF were detected by RT-PCR and Western blot tests. Immunofluorescence staining were used to determine the expressions of DNMT1 and DNMT3a. The quantitative methylation analysis of the 11 CpG island of the promoter region of BDNF exon IV was determined using the Agena's MassARRAY EpiTYPER system. We found that 2% H 2 inhalation can reduce pro-inflammatory factors, alleviate DNMT1, DNMT3a but not DNMT3b expression, make hypomethylation of BDNF promoter IV at 5 CpG sites, enhance the BDNF levels and then decrease escape latency but increase platform crossing times in septic mice. Our results suggest that 2% H 2 inhalation may alleviate SAE through altering the regulation of BDNF promoter IV methylation which mediated by DNMT1 and DNMT3a in the hippocampus of septic mice. [ABSTRACT FROM AUTHOR]