Search

Brain-derived neurotrophic factor (BDNF) is a growth factor that plays vital roles in the neuron survival, growth, and neuroplasticity. Alteration to BDNF expression is associated with major depressive disorder. However, the BDNF translational machinery in depression remains unknown. Herein, we pointed that Pdcd4, a suppressor oncogene, acted as an endogenous inhibitor for the translation of BDNF, and selectively repressed the translation of BDNF splice variant IIc mRNA in an eIF4A-dependent manner. Chronic restraint stress (CRS) up-regulated Pdcd4 expression in hippocampus via decreasing mTORC1-mediated proteasomes degradation pathway, which resulted in the reduction of BDNF protein expression. Moreover, over-expression of Pdcd4 in the hippocampus triggered spontaneous depression-like behaviors under the non-stressed conditions in mice, while systemic or neuron-specific knockout of Pdcd4 reverses CRS-induced depression-like behaviors. Importantly, administration of Pdcd4 siRNA or an interfering peptide that interrupts the Pdcd4-eIF4A complex substantially promoted BDNF expression and rescued the behavioral disorders which were caused by CRS. Overall, we have discovered a previously unrecognized role of Pdcd4 in controlling BDNF mRNA translation, and provided a new method that boosting BDNF expression through blocking the function of Pdcd4 in depression, indicating that Pdcd4 might be a new potential target for depressive disorder therapy.

Current control of pathogenic bacteria at all biomaterial interfaces is poorly attuned to a broad range of disease-causing pathogens. Leading antimicrobial surface functionalization strategies with antimicrobial peptides (AMPs), defensins, have not shown their promised efficacy. One of the main problems is the lack of stability and swift clearance from the surface. Surface nanotopography bearing sharp protrusions is a non-chemical solution that is intrinsically stable and long-lasting. Previously, the geometrically ordered arrays of nanotipped spines repelled or rapidly ruptured bacteria that come into contact. The killing properties so far work on cocci and rod-like bacteria, but there is no validation of the efficacy of protrusional surfaces on pathogenic bacteria with different sizes and morphologies, thus broadening the utility of such surfaces to cover increasingly more disease entities. Here, we report a synthetic analogue of nanotipped spines with a pyramidal shape that show great effectiveness on species of bacteria with strongly contrasting shapes and sizes. To highlight this phenomenon in the field of dental applications where selective bacterial control is vital to the clinical success of biomaterial functions, we modified the poly(methyl)-methacrylate (PMMA) texture and tested it against Streptococcus mutans, Enterococcus faecalis, Porphyromonas gingivalis, and Fusobacterium nucleatum. These nanopyramids performed effectively at levels well above those of normal and roughened PMMA biomaterials for dentistry and a model material for general use in medicine and disease transmission in hospital environments.

Depression is one of the most common psychiatric disorders. Recently, studies demonstrate that antidepressants generating BDNF not only maintain synaptic signal transmission but also repress neuroinflammatory cytokines such as IL-6 and IL-1β. Therefore, promoting BDNF expression provides a strategy for the treatment of depression. Our recent research has indicated that programmed cell death 4 (Pdcd4) is a new target for antidepressant treatment by facilitating BDNF. Herein, we modified Pdcd4 specific small interfering RNA (siPdcd4) with the rabies virus glycoprotein peptide (RVG/siPdcd4) which enables it cross the blood-brain barrier (BBB). We found that RVG/siPdcd4 complex was selectively delivered to neurons and microglia and silenced the expression of Pdcd4, thereby up-regulating the level of BDNF and down-regulating IL-6 and IL-1β expression. More importantly, RVG/siPdcd4 injection attenuated synaptic plasticity impairment and protected mice from CRS-induced depressive behavior. These findings suggest that RVG/siPdcd4 complex is a potential therapeutic medicine for depression.

Objectives The purpose of this study was to estimate the fatigue life of premolars restored with two dental ceramics, lithium disilicate (LD) and polymer infiltrated ceramic (PIC) using the numerical method and compare it with the published in vitro data. Methods A premolar restored with full-coverage crown was digitized. The volumetric shape of tooth tissues and crowns were created in Mimics®. They were transferred to IA-FEMesh for mesh generation and the model was analyzed with Abaqus. By combining the stress distribution results with fatigue stress–life (S–N) approach, the lifetime of restored premolars was predicted. Results The predicted lifetime was 1,231,318 cycles for LD with fatigue load of 1400 N, while the one for PIC was 475,063 cycles with the load of 870 N. The peak value of maximum principal stress occurred at the contact area (LD: 172 MPa and PIC: 96 MPa) and central fossa (LD: 100 MPa and PIC: 64 MPa) for both ceramics which were the most seen failure areas in the experiment. In the adhesive layer, the maximum shear stress was observed at the shoulder area (LD: 53.6 MPa and PIC: 29 MPa). Significance The fatigue life and failure modes of all-ceramic crown determined by the numerical method seem to correlate well with the previous experimental study.

Background Social differences for individuals with autism spectrum disorder (ASD) could be related to attentional bias toward threatening emotional faces. However, studies investigating this attentional bias in individuals with ASD vary in paradigms and results. Methods We conducted a meta-analysis across different reaction time tasks, including dot-probe, spatial cuing, visual search and emotional Stroop tasks, to examine the attentional bias toward threatening emotional faces in individuals with ASD. Narrative synthesis further summarized possible moderators affecting attentional bias. Results We used systematic searches to identify 21 empirical studies with 1,805 participants in total (ASD n = 909). Individuals with ASD showed a small but significant attentional bias toward threatening emotional faces over other faces (g = 0.162), which was similar to individuals with typical development (g = 0.203). Moderator analysis showed that adults with ASD showed a larger attentional bias than children with ASD. For the dot-probe and spatial cuing paradigms, attentional bias toward threatening emotional faces was observed when stimuli were presented for less than 500 ms, and bias away from threatening emotional faces was shown when stimuli were presented for over 500 ms. For the visual search paradigm, attentional bias was significant in button-press tasks, but not in touch-screen tasks. Furthermore, attentional bias was only observed when the stimuli were schematic faces and reference materials were happy faces. Conclusions Individuals with ASD showed a small but significant attentional bias toward threatening emotional faces. Furthermore, significant moderators included stimulus presentation, response type, reference face type, stimulus type, and age. Thus, more research is needed to further explore attentional bias toward threatening emotional faces in individuals with ASD.

nbsp nbsp Background It is still difficult to perform pedicle screw insertion on patients with abnormal spine morphology There is an urgent need to provide projection fluoroscopy images to surgeons to practice pedicle screw insertion nbsp nbsp Methods The simulation software uses a volume rendering algorithm to generate a three dimensional spine and it uses a digitally reconstructed radiograph algorithm to simulate anteroposterior and lateral radiographs as the intraoperative image for minimally invasive surgery nbsp nbsp Results Pedicle screw insertion can be accomplished using a bone drill and multidimensional pedicle screws and can be exhibited or evaluated in both two and three dimensions Simultaneously advanced expert preoperative planning can be shown in system nbsp nbsp Conclusion A simulator that develops a three dimensional patient specific volume rendered simulation combined with the projection fluoroscopy for pedicle screw insertion is introduced The simulator can help the surgeon to plan the operation trajectory and can help to predict the complex situation of the operation

The aim of the study was to examine the correlation between KCNJ11 gene polymorphism and metabolic syndrome in elderly patients. From January 2014 to January 2015, 54 elderly patients with metabolic syndrome were enrolled in this study as the observation group. During the same period, 46 healthy elderly individuals were enrolled in this study as the control group. KCNJ11 gene polymorphism (rs28502) was analyzed using polymerase chain reaction-restriction fragment length polymorphism. The expression levels of mRNA in different genotypes were detected using FQ-PCR. ELISA was used to evaluate the KCNJ11 protein expression in different genotypes. KCNJ11 gene polymorphism and metabolic syndrome was studied by measuring the blood pressure levels in patients with different genotypes. Three genotypes of KCNJ11 gene in rs28502 were CC, CT and TT. The CC, CT and TT genotype frequencies in healthy population were 8.5, 9.2 and 82.2%, respectively, while the genotype frequencies in patients with metabolic syndrome were 42.4, 49.8 and 7.8%, respectively. There were significant differences between groups (P≤0.05). However, the genotype frequencies of C/T in healthy individuals and metabolic syndrome patients were 35.3 and 38.3%, respectively. There were no significant differences between groups (P>0.05). FQ-PCR results showed that the KCNJ11 mRNA expression levels in the control and observation groups had no significant differences (P>0.05). However, the results obtained from ELISA analysis revealed that KCNJ11 protein expression level in the observation group was significantly higher than that in the control group (P

OBJECTIVE To evaluate whether the combination of magnetic resonance spectroscopy (MRS) and ¹¹C-methionine positron emission tomography (¹¹C-MET PET) could increase accurate diagnostic sensitivity for non-enhancing supratentorial gliomas. MATERIALS AND METHODS Between February 2012 and December 2017, 109 patients with non-enhanced supratentorial lesions on contrast-enhanced MRI were enrolled. Each patient underwent MRS and ¹¹C-MET PET before treatment. A lesion was considered to be a glioma when either the MRS or ¹¹C-MET PET results reached the diagnostic threshold. The radiological diagnosis was compared with the pathological diagnosis or medical diagnostic criteria. RESULTS The sensitivity and specificity were 60.0% and 50.0% for MRS and 75.8% and 50.0% for ¹¹C-MET PET, respectively. Upon combining the two modalities, the sensitivity and specificity of the imaging-based diagnosis prior to surgery reached 89.5% and 42.9%, respectively. Statistically significant differences in the sensitivities were observed between the combined and individual approaches (MRS alone, 89.5% vs. 60.0%, p < 0.001; ¹¹C-MET PET alone, 89.5% vs. 75.8%, p = 0.001). However, no significant differences in specificity were observed between the combined and individual modalities. CONCLUSION The combination of MRS and ¹¹C-MET PET findings significantly increases accurate diagnostic sensitivity for non-enhancing supratentorial gliomas without significantly lowering the specificity. This finding suggests the potential of the combined MRS and ¹¹C-MET PET approach in clinical applications.

Objectives: This study aimed to review etiological and epidemiological data for hand, foot, and mouth disease (HFMD) cases that occurred between 2008 and 2010 in Guangzhou City, to help develop and implement precautionary measures applicable for future outbreaks. Methods: The characteristics of 4,753 HFMD episodes were retrospectively reviewed in 4,636 patients reported between 2008 and 2010 by the Guangdong Women and Children's Hospital, which is the national enterovirus monitoring agent and the designated hospital in China for treating severe HFMD. Results: Out of 4,753 incident episodes reviewed, 525 patients were hospitalized; 60% were males. Most patients (93.8%) were children under 5 years old, with a median age at onset of 2.4 years. HFMD incidence peaked in April/May and September/October. From the total, 1,067 (22.4%) infections were positive for human enterovirus 71 (HEV71), 1,094 (23.0%) were positive for coxsackievirus A16 (CA16), and 941 (19.8%) were positive for other common enteroviruses. In contrast, 1,666 (35.0%) cases were negative to HEV71, CA16, and other common enteroviruses. Cross-correlation coefficients demonstrated associations between the number of cases, seasonal temperatures, and humidity. Among hospitalized cases, HEV71 was positive in 261 (24.5%), and 42 (3.9%) critical cases were positive for HEV71. Conclusion: Seasonal fluctuations and HEV71 and CA16 were the two key factors influencing the Guangzhou HFMD epidemic. The infection predominantly affected children younger than 5 years old. Keywords: Epidemic, Hand, foot and mouth disease, Coxsackie virus A16, Human enterovirus 71

OBJECT The extent of resection is one of the most essential factors that influence the outcomes of glioma resection. However, conventional structural imaging has failed to accurately delineate glioma margins because of tumor cell infiltration. Three-dimensional proton MR spectroscopy (1H-MRS) can provide metabolic information and has been used in preoperative tumor differentiation, grading, and radiotherapy planning. Resection based on glioma metabolism information may provide for a more extensive resection and yield better outcomes for glioma patients. In this study, the authors attempt to integrate 3D 1H-MRS into neuronavigation and assess the feasibility and validity of metabolically based glioma resection. METHODS Choline (Cho)–N-acetylaspartate (NAA) index (CNI) maps were calculated and integrated into neuronavigation. The CNI thresholds were quantitatively analyzed and compared with structural MRI studies. Glioma resections were performed under 3D 1H-MRS guidance. Volumetric analyses were performed for metabolic and structural images from a low-grade glioma (LGG) group and high-grade glioma (HGG) group. Magnetic resonance imaging and neurological assessments were performed immediately after surgery and 1 year after tumor resection. RESULTS Fifteen eligible patients with primary cerebral gliomas were included in this study. Three-dimensional 1H-MRS maps were successfully coregistered with structural images and integrated into navigational system. Volumetric analyses showed that the differences between the metabolic volumes with different CNI thresholds were statistically significant (p < 0.05). For the LGG group, the differences between the structural and the metabolic volumes with CNI thresholds of 0.5 and 1.5 were statistically significant (p = 0.0005 and 0.0129, respectively). For the HGG group, the differences between the structural and metabolic volumes with CNI thresholds of 0.5 and 1.0 were statistically significant (p = 0.0027 and 0.0497, respectively). All patients showed no tumor progression at the 1-year follow-up. CONCLUSIONS This study integrated 3D MRS maps and intraoperative navigation for glioma margin delineation. Optimum CNI thresholds were applied for both LGGs and HGGs to achieve resection. The results indicated that 3D 1H-MRS can be integrated with structural imaging to provide better outcomes for glioma resection.

Summary Background Human cytomegalovirus (HCMV) is a leading cause of morbidity and mortality in immunocompromised individuals. The unique long b’ (ULB’) region of HCMV contains at least 19 open reading frames (ORFs); however, little is known about the function of UL145 and UL136. We characterized UL145 and UL136 in low-passage clinical isolates from Chinese infants. Material/Methods The clinical strains of HCMV were recovered from the urine from HCMV-infected infants. Human embryonic lung fibroblasts (HELFs) were infected with clinical isolates of HCMV, and the viral DNA and mRNA for UL145 and UL136 were analyzed by polymerase chain reaction (PCR) and sequencing techniques. We also predicted the structure and function of UL145 and UL136 proteins. Results Sixty-two Chinese infants infected with HCMV were recruited into this study and the clinical isolates were recovered from the urine. Two strains among the low-passage isolates, D2 and D3, were obtained. The UL145 and UL136 sequences were deposited with GenBank under accession numbers of DQ180367, DQ180381, DQ180377, and DQ180389. The mRNA expression of both UL145 and UL136 was confirmed by reverse transcription (RT-PCR) assays. UL145 was predicted to contain 1 protein kinase C phosphorylation site, 2 casein kinase II phosphorylation sites and a zinc finger structure. UL136 was predicted to contain a protein kinase C phosphorylation site, N-myristoylation site, cAMP- and cGMP-dependent protein kinase phosphorylation site and tyrosine kinase II phosphorylation site. Both UL145 and UL136 are highly conserved. Conclusions UL145 may act as an intranuclear regulating factor by direct binding to DNA, while UL136 may be a membrane receptor involving signal transduction.

Purpose: To isolate and characterize primary fetus retinal microvascular endothelial cells (RMECs) in order to facilitate the study of their properties in vitro. Methods: Human RMECs were isolated from abortive fetuses whose gestational ages were between 20 and 28 weeks by mechanical morcel and trypsin-collagenase digestion, plated on fibronectin-coated wells and purified gradually in high-selective condition. The RMECs were characterized for expression and localization of endothelial cell markers by indirect immunocytochemical staining of von Willebrand factor (vWF) and CD34, the distribution of cell markers was observed by confocal immunofluorescence microscope. The ability of these cells to form capillary-like networks was assessed subsequently. Cobalt dichloride (CoCl2) was used to simulate hypoxia in the culture condition and Western blot was used to detect the alternation of VEGF protein level under normoxia and hypoxia. Results: Isolation of fetus RMECs has been very difficult and primary culture of these special premature RMECs has not been previously reported due to many reasons. Here we established a simple and convenient method for the primary culture of fetus human RMECs. Our results show that delicate RMECs could be obtained readily and grow very fast, and the purity of RMECs was up to 95% demonstrated by specific staining for vWF in the cytoplasm. Our research also indicates that nearly 100% of cells could express CD34. The cells were successfully passaged and maintained in culture for 5–7 passages without a significant loss in expression of endothelia cell markers. The fetus RMECs formed capillary-like networks on the Matrigel well. Expression of VEGF protein increased significantly under hypoxia. Conclusions: Pure fetus RMECs could be obtained rapidly and easily by our method.Fetus RMECs have some specific properties. Hypoxia could induce expression of VEGF. Cell properties related with age of the donors should be considered while studying in vitro, especially in some age-specific diseases such as retinopathy of prematurity and diabetic retinopathy.

Massively parallel sequencing (MPS) of cell-free fetal DNA from maternal plasma has revolutionized our ability to perform noninvasive prenatal diagnosis. This approach avoids the risk of fetal loss associated with more invasive diagnostic procedures. The present study developed an effective method for noninvasive prenatal diagnosis of common chromosomal aneuploidies using a benchtop semiconductor sequencing platform (SSP), which relies on the MPS platform but offers advantages over existing noninvasive screening techniques. A total of 2,275 pregnant subjects was included in the study; of these, 515 subjects who had full karyotyping results were used in a retrospective analysis, and 1,760 subjects without karyotyping were analyzed in a prospective study. In the retrospective study, all 55 fetal trisomy 21 cases were identified using the SSP with a sensitivity and specificity of 99.94% and 99.46%, respectively. The SSP also detected 16 trisomy 18 cases with 100% sensitivity and 99.24% specificity and 3 trisomy 13 cases with 100% sensitivity and 100% specificity. Furthermore, 15 fetuses with sex chromosome aneuploidies (10 45,X, 2 47,XYY, 2 47,XXX, and 1 47,XXY) were detected. In the prospective study, nine fetuses with trisomy 21, three with trisomy 18, three with trisomy 13, and one with 45,X were detected. To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using the SSP and provides an effective strategy for large-scale noninvasive screening for chromosomal aneuploidies in a clinical setting.

Evidence suggests that smoking adversely affects bones. Glutathione S-transferases (GSTs) are important in the detoxification of tobacco smoke compounds. This study investigated the influence of GSTM1 and GSTT1 genetic polymorphisms on the effects on bone induced by tobacco smoking in young men. In total, 231 Chinese men aged 20-39 years were assessed by a cross-sectional study. Calcaneal quantitative ultrasound (QUS) was measured. Smoking information was obtained using a questionnaire. Genotypes were determined for null alleles of GSTM1 and GSTT1. Smoking was inversely associated with speed of sound (SOS) and bone quality index (BQI) among subjects with GSTM1 null genotype (β = -0.28, 95% CI, -34.01 to -8.65 and β = -0.30, 95% CI, -16.41 to -4.49, respectively), but not among those with the allele present (β = -0.02, 95% CI, -15.01 to 12.59 and β = -0.09, 95% CI, -8.75 to 3.02, respectively). P for interaction = 0.04 for SOS and 0.08 for BQI. No interaction was found between the GSTT1 polymorphism and smoking. The results showed that GSTM1 deficiency may increase the adverse effect of smoking on calcaneal QUS in young men, suggesting an interaction between metabolic genes and tobacco smoke in bone detoxification.

Background The noninvasive prenatal diagnosis procedures that are currently used to detect genetic diseases do not achieve desirable levels of sensitivity and specificity. Recently, fetal methylated DNA biomarkers in maternal peripheral blood have been explored for the noninvasive prenatal detection of genetic disorders. However, such efforts have covered only chromosomal aneuploidy, and fetal methylated DNA biomarkers in maternal whole blood for detecting single-gene diseases remain to be discovered. Methods To address this issue, we systematically screened significantly hypermethylated genes in fetal tissues and compared them with maternal peripheral blood potential in an attempt to detect fetal genes in maternal peripheral blood. First, the methylated-CpG island recovery assay combined with a CpG island array was performed for four fetus-toward placental tissues and the corresponding maternal peripheral bloods. Subsequently, direct bisulfite sequencing and combined bisulfite restriction analysis (COBRA) were carried out to validate the methylation status of the hypermethylated genes that were identified by the microarray analysis. Results Three hundred and ten significantly hypermethylated genes in the placental tissues were detected by microarray. From the top 15 hypermethylated genes detected by microarray, two were selected for sequencing validation in placental tissue and chorionic villus samples and four were selected for COBRA validation in four placental tissues, ten amniotic fluids and five chorionic villus samples. The six selected genes were confirmed to be hypermethylated in placental tissue and chorionic villus samples, but methylation of the genes could not be detected in the amniotic fluids. Conclusions Of the many hypermethylated genes and methylation sites that were found in the fetal tissues, some have great potential to be developed into molecular markers for noninvasive prenatal diagnosis of monogenic disorders. Further clinical studies are warranted to confirm these findings.

Objective: The study was to observe the effect of polymer-PS (Curosurf)mixtures on acute lung injury rats with E.coli. Methods: Adult rats given 3ml/kg 3x109CFU/ml E.coli by tracheal, were mechanically ventilated after infection for 24~36h. Fifteen minutes later, the animals with ALI (PaO2 < 20.kPa) were randomly divided into six treatment groups by transtrachea instillation (1) NS group (2) PS group (3) PS+NS group (4) PS+ PEG group (5) PS+ Dextran group (6) PS+ HA group. The blood gas analysis were measured in the pre-or post-treatment during 180 min. At the end, MIP-2 in the right lung lavage fluid were performed. Result: At 180 min post-treatment, PaO2 of all PS or PS-polymer treatment groups increased compared with pre-treatment, but they were less than normal control group (p< 0.01), PaO2 of PS, PS+ Dextran, PS+HA group were singnificantly more than that of the NS group (p< 0.01 or 0.05) respectively. MIP-2 of lung lavage fluid in all treatment groups were higher than that of normal group (p< 0.01 or 0.05). MIP-2 of PS, PS+PEG, PS+ Dextran, PS+ HA group were less than that of NS group (p< 0.01) respectively except PS+NS group. Conclusions: The data suggest that PS, PS+Dextran and PS+HA improved oxygenation function in ventilated rats with ALI induced by E.Coli. and the PS-polymer mixtures seemed more effective in inhibiting MIP-2 than PS in the same dose. Further preclinical studies are required.