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Gender and sex differences in pain recognition and drug responses have been reported in clinical trials and experimental models of pain. Among antidepressants, contradictory results have been observed in patients treated with selective serotonin reuptake inhibitors (SSRIs). This study evaluated sex differences in response to the SSRI fluoxetine after chronic administration in the mouse formalin test. Adult male and female CD1 mice were intraperitoneally injected with fluoxetine (10 mg/kg) for 21 days and subjected to pain assessment. Fluoxetine treatment reduced the second phase of the formalin test only in female mice without producing behavioral changes in males. We also observed that fluoxetine was able to specifically increase the expression of metabotropic glutamate receptor type-2 (mGlu2) in females. Also a reduced expression of the epigenetic modifying enzyme, histone deacetylase 2 (HDAC2), in dorsal root ganglia (DRG) and dorsal horn (DH) together with an increase histone 3 acetylation (H3) level was observed in females but not in males. With this study we provide evidence that fluoxetine induces sex specific changes in HDAC2 and mGlu2 expression in the DH of the spinal cord and in DRGs and suggests a molecular explanation for the analgesic effects in female mice. [ABSTRACT FROM AUTHOR]

Abstract Background MiRNAs play important roles in the development of ovarian cancer, activation of primitive follicles, follicular development, oocyte maturation and ovulation. In the present study, we investigated the specific role of miR-23a in cov434 cells. Results Downregulation of miR-23a was observed in serum of PCOS patients compared with the healthy control, suggesting the inhibitory effect of miR-23a in PCOS. MiR-23a was positively correlated with Body Mass Index (BMI) and negatively correlated with Luteinizing hormone (LH), Testostrone (T), Glucose (Glu) and Insulin (INS) of PCOS patients. MiR-23a mimic inhibited the proliferation and promoted apoptosis of human cov434 cells. In addition, flow cytometry assay confirmed that miR-23a blocked cell cycle on G0/G1 phase. MiR-23a inhibitor showed opposite results. Furthermore, double luciferase reporter assay proved that miR-23a could bind to the 3’UTR of FGD4 directly through sites predicted on Target Scan. FGD4 level was significantly suppressed by miR-23a mimic, but was significantly enhanced by miR-23a inhibitor. We further proved that miR-23a increased the expression of activated CDC42 (GTP bround) and p-PAK-1, suggesting that miR-23a induced cell cycle arrest through CDC42/PAK1 pathway. Conclusions In conclusion, our study reveals that miR-23a participates in the regulation of proliferation and apoptosis of cov434 cells through target FGD4, and may play a role in the pathophysiology of PCOS.

Here the authors show a beta alumina nanowires/gel polymer composite electrolyte design. The dense and homogeneous solid-liquid hybrid sodium-ion transportation channels promote uniform sodium deposition and stripping and significantly improve the performance of a Na metal battery.

Abstract Background Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker of early diagnosis and prediction for acute kidney injury (AKI). However, the current program for NGAL detection is not extensively applied in clinics due to the high expense of antibodies. Nucleic acid aptamers are single-strand DNAs or RNAs which could bind to targets with high specificity and affinity, and they have been widely used in the diagnosis and therapy for multiple diseases. It is valuable for us to develop a new method for NGAL detection using aptamers instead of antibodies to achieve increased efficiency and decreased cost. Methods Nucleic acid aptamers against NGAL were obtained after SELEX process using magnetic beads, and an enzyme-linked aptamer analysis (ELAA), which can be widely used in clinical diagnosis at low cost, were successfully established. The feasibility of ELAA was further validated with urine samples harvested from 43 AKI patients and 30 healthy people. Results Three candidate aptamers, including NA36, NA42 and NA53, were obtained after 8 rounds of SELEX process with magnetic beads and verified by quantitative polymerase chain reaction (qPCR), and the Kd value of each aptamer was 43.59, 66.55 and 32.52 nM, respectively. Moreover, the linear relationship was consistent at the range of 125–4000 ng/mL, and the detection limit of ELAA assay was 30.45 ng/mL. We also found that NGAL could be exclusively detected with NA53, and no cross-reaction between NA53 and human albumin or globulin occurred, the coefficient of variation (CV) between inner-plate and inter-plate was less than 15%, and the recovery rate was between 80 and 110%. Moreover, the sensitivity and specificity of ELAA assay in this study are 100% and 90%, respectively. Consistently, these results could also diagnose whether the occurrence of AKI in lots of patients, which has been demonstrated with the ELAA method we established after using NA53. Conclusions Taken together, NA53, the best candidate aptamer targeting NGAL protein, can be applied in clinical testing.

In this study, our aim was to estimate the extent of Yersinia enterocolitica contamination in frozen foods in China and determine the bioserotype, virulotype, antimicrobial resistance, and enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) genotyping profiles of recovered Y. enterocolitica isolates. Out of 455 samples collected between July 2011 and May 2014, 56 (12.3%) tested positive for Y. enterocolitica. The 70 isolated strains were grouped into five clusters and one singleton based on their ERIC-PCR fingerprint, at a similarity coefficient of 70%. All strains were of biotype 1A, and 35.7% were of bioserotype 1A/O:8. Most strains lacked the virulence genes ail, virF, ystA, and ystC, but harbored ystB, fepD, ymoA, fes and sat. All strains were sensitive to ticarcillin but resistant to two or more antibiotics, and 48.6% of the strains were resistant to four to nine antibiotics. High resistance rates were observed for ampicillin, cephalothin, trimethoprim/sulfamethoxazole, amoxicillin/clavulanic acid, nalidixic acid and chloramphenicol (98.6%, 95.7%, 74.3%, 28.6%, 18.6% and 12.9%, respectively). This study provides a systematic surveillance of Y. enterocolitica prevalence in frozen foods in China and indicates its high antibiotic resistance, which could serve as useful information for the government to control Y. enterocolitica contamination in frozen foods and the use of antibiotics. [ABSTRACT FROM AUTHOR]

Abstract Background Osteogenesis imperfecta (OI) type V is a rare heritable bone disorder caused by pathogenic variants of IFITM5. Only two mutated alleles in IFITM5 have been identified worldwide, the role of which in OI pathology is not fully understood. Methods A neonatal case of suspected OI, clinically manifested as a rare clavicle transection fracture with delayed early fracture healing, was studied. Subtle variants of OI‐associated genes were analyzed by whole exome sequencing and confirmed by Sanger sequencing. Results A de novo heterozygous pathogenic variant of IFITM5 within the 5′‐UTR (c.‐9C > A) was discovered in the proband. Bioinformatics analysis using a combination of various algorithms predicted that the variant would generate a new in‐frame start codon 9 bp upstream of the original and express a mutant IFITM5 protein with three additional amino acids (Met‐Glu‐Pro). After transfection into a eukaryocyte in vitro, the mutant IFITM5 construct produced a longer transcription product than that of wild‐type IFITM5. Conclusion This study identified a novel pathogenic variant of IFITM5, which not only manifested the molecular characteristics of IFITM5, but also provided new evidence for the study of the molecular mechanisms of IFITM5 association with OI.

Neuropathic pain resulting from nerve lesions or dysfunction represents one of the most challenging neurological diseases to treat. A better understanding of the molecular mechanisms responsible for causing these maladaptive responses can help develop novel therapeutic strategies and biomarkers for neuropathic pain. We performed a miRNA expression profiling study of dorsal root ganglion (DRG) tissue from rats four weeks post spinal nerve ligation (SNL), a model of neuropathic pain. TaqMan low density arrays identified 63 miRNAs whose level of expression was significantly altered following SNL surgery. Of these, 59 were downregulated and the ipsilateral L4 DRG, not the injured L5 DRG, showed the most significant downregulation suggesting that miRNA changes in the uninjured afferents may underlie the development and maintenance of neuropathic pain. TargetScan was used to predict mRNA targets for these miRNAs and it was found that the transcripts with multiple predicted target sites belong to neurologically important pathways. By employing different bioinformatic approaches we identified neurite remodeling as a significantly regulated biological pathway, and some of these predictions were confirmed by siRNA knockdown for genes that regulate neurite growth in differentiated Neuro2A cells. In vitro validation for predicted target sites in the 39-UTR of voltage-gated sodium channel Scn11a, alpha 2/ delta1 subunit of voltage-dependent Ca-channel, and purinergic receptor P2rx ligand-gated ion channel 4 using luciferase reporter assays showed that identified miRNAs modulated gene expression significantly. Our results suggest the potential for miRNAs to play a direct role in neuropathic pain. [ABSTRACT FROM AUTHOR]

Xiud Yax Lus Qim or Yalu wang 亞魯王 (Ode to the King Yalu) is a type of oral performance inherited verbally and transmitted orally by dongb langf (donglang 東郎, chanters of Yalu wang) at funerals and festive occasions. As one of the most representative cultural sets of the Miao (Hmong) ethnic group located in southern China, Yalu wang is embedded in Miao sorcery beliefs and practices, and serves as a vehicle to unite the community and maintain the identity of the ethnic group. However, since Yalu wang was “discovered” as a heroic epic by scholars in 2009 and entered the government’s “List of National Intangible Cultural Heritage” two years later, different agencies have been vying to appropriate its cultural resources. Not only do local government authorities use it as a tourist attraction, stage performances have also produced various versions of Yalu wang to portray an emblem of what are presumed to be “authentic Miao cultures”. This article explores the interactive relationship between Miao sorcery and folk traditions in the oral performance of Yalu wang and their enactment and re-enactment in theatrical performances under the aegis of a state-endorsed tourism policy. In so doing, the discussion sheds new light on the bidirectional dynamics that not only remold the style of performing culture, but also facilitate religious synthesis.

Summary: The mechanistic target of rapamycin complex 2 (mTORC2) coordinates cell proliferation, survival, and metabolism with environmental inputs, yet how extracellular stimuli such as growth factors (GFs) activate mTORC2 remains enigmatic. Here we demonstrate that in human endothelial cells, activation of mTORC2 signaling by GFs is mediated by transmembrane cell adhesion protein CD146. Upon GF stimulation, the cytoplasmic tail of CD146 is phosphorylated, which permits its positively charged, juxtamembrane KKGK motif to interact with Rictor, the defining subunit of mTORC2. The formation of the CD146-Rictor/mTORC2 complex protects Rictor from ubiquitin-proteasome-mediated degradation, thereby specifically upregulating mTORC2 activity with no intervention of the PI3K and mTORC1 pathways. This CD146-mediated mTORC2 activation in response to GF stimulation promotes cell proliferation and survival. Therefore, our findings identify a molecular mechanism by which extracellular stimuli regulate mTORC2 activity, linking environmental cues with mTORC2 regulation. : Xu et al. demonstrate that the transmembrane adhesion molecule CD146 interacts with and stabilizes the mTORC2 core subunit Rictor in response to growth factor stimulation, thereby acting as an upstream regulator for mTORC2 activation. Therefore, this study identifies a molecular mechanism integrating environmental cues with mTORC2 activity. Keywords: mTORC2, Rictor, CD146, PI3K, mTORC1, signal transduction, cell proliferation

Objective. To study the effects of low-dose and long-term treatment with erythromycin on IL-17 and IL-23, in peripheral blood and induced sputum, in patients with stable chronic obstructive pulmonary disease (COPD). Methods. Patients were randomly divided into placebo-treated group, group A (12 months of additive treatment with erythromycin, N=18), and group B (6 months of additive treatment with erythromycin followed by 6 months of follow-up, N=18). Inflammatory cells in induced sputum, pulmonary function, and the 6-minute walk distance (6MWD) were analyzed. Concentrations of IL-17 and IL-23 in peripheral blood and sputum were measured using enzyme-linked immunosorbent assays. Results. After treatment, sputum and peripheral blood concentrations of IL-17 and IL-23 significantly decreased in groups A and B compared with placebo-treated group. There were no significant differences after erythromycin withdrawal at months 9 and 12 in group B compared with placebo-treated group. An increase in 6MWD was observed after treatment. Conclusions. Erythromycin was beneficial and reduced airway inflammation in COPD patients. Underlying mechanisms may involve inhibition of IL-17 and IL-23 mediated airway inflammation. COPD patients treated with erythromycin for 6 months experienced improved exercise capacity. Finally, treatment for 12 months may be more effective than treatment for 6 months.

Energy efficiency is one of the most practical ways for China to simultaneously tackle environmental issues and achieve sustainable development. However, the issue of inadequate capital inflows is a bottleneck in energy efficiency projects, especially for small and medium-sized enterprises (SMEs). This study focuses on the complicated financial barriers to effectively promoting such projects for SMEs. A hybrid framework was proposed to recognize the most obvious financing barriers under uncertain circumstances. Potential barriers were collected firstly to build an index system, including the five dimensions of “policy and regulation”, “economic market”, “financial institutions”, “behavior” and “economic non-market”. Then, this paper introduced a novel way to combine a fuzzy Delphi and a fuzzy decision making trial and evaluation laboratory (DEMATEL) method. The fuzzy Delphi method was applied to extract significant factors from potential barriers. To analyze a series of causal relationships, the fuzzy DEMATEL approach was employed. Moreover, triangular fuzzy numbers (TFNs) are used firstly to express vague linguistic ratings in the proposed framework. Based on the experts’ opinions, seventeen significant factors were chosen to assemble a final evaluation system. Eleven key barriers were identified by analyzing cause-effect relations, including “slight fiscal incentives”, “inadequate energy market trading mechanisms”, “a low priority of energy saving issues”, etc. The key barriers affiliated with “market” and “policy and regulation” are much more important than the others. Except for B11 and B53, the others are the original factors. Finally, we listed relevant suggested measures to help SMEs, government departments and financial institutions overcome the key barriers.

Ochratoxin A (OTA) is a mycotoxin which is a common contaminant in grains during storage. Aspergillus ochraceus is the most common producer of OTA. Essential oils play a crucial role as a biocontrol in the reduction of fungal contamination. Essential oils namely natural cinnamaldehyde, cinnamon oil, synthetic cinnamaldehyde, Litsea citrate oil, citral, eugenol, peppermint, eucalyptus, anise and camphor oils, were tested for their efficacy against A. ochraceus growth and OTA production by fumigation and contact assays. Natural cinnamaldehyde proved to be the most effective against A. ochraceus when compared to other oils. Complete fungal growth inhibition was obtained at 150-250 µL/L with fumigation and 250-500 µL/L with contact assays for cinnamon oil, natural and synthetic cinnamaldehyde, L. citrate oil and citral. Essential oils had an impact on the ergosterol biosynthesis and OTA production. Complete inhibition of ergosterol biosynthesis was observed at ≥ 100 µg/mL of natural cinnamaldehyde and at 200 µg/mL of citral, but total inhibition was not observed at 200 µg/mL of eugenol. But, citral and eugenol could inhibit the OTA production at ≥ 75 µg/mL and ≥ 150 µg/mL respectively, while natural cinnamaldehyde couldn't fully inhibit OTA production at ≤ 200 µg/mL. The inhibition of OTA by natural cinnamaldehyde is mainly due to the reduction in fungal biomass. However, citral and eugenol could significant inhibit the OTA biosynthetic pathway. Also, we observed that cinnamaldehyde was converted to cinnamic alcohol by A. ochraceus, suggesting that the antimicrobial activity of cinnamaldehyde was mainly attributed to its carbonyl aldehyde group. The study concludes that natural cinnamaldehyde, citral and eugenol could be potential biocontrol agents against OTA contamination in storage grains.