PurposeTo estimate the prevalence of myopia among primary and middle school-aged students in Guangzhou and to explore the potentially contributing factors to myopia.MethodsThis cross-sectional study ...was based on a sample of students in grades 1-6 and grades 7-9. Data were collected from refractive error measurements and a structured questionnaire.ResultsA total of 3055 participants were involved in this analysis, and the overall prevalence of myopia was 47.4% (95% confidence interval (CI)= 45.6-49.2%). The prevalence of myopia in students increased along with the growth of grade level; the prevalence of myopia in students in grade 1 was only 0.2%, as it increased to 38.8% in students in grade 3, and the rate was the highest (68.4%) in students in grade 9. Girls were at a higher risk of myopia than boys (adjusted odds ratio=1.22, 95% CI=1.04-1.44). Both male and female students whose distance of reading was longer than 25 cm were less likely to have myopia and who have one or two myopic parents were at a higher risk of myopia. In addition, reading for pleasure more than 2 h per day (adjusted odds ratio=1.84, 95% CI=1.09-3.12) was only positively associated with myopia in boys and spending time watching television per week was only positively associated with myopia in girls.ConclusionMyopia in students is a significant public health problem in Guangzhou. Female gender, higher grade, longer time spent for near work, shorter distance of near work, and parental myopia were shown to be associated with the increasing risk of myopia in children.
A highly selective arylation of a number of polyaromatic hydrocarbons (PAHs) with aryliodonium salts and Pd/C as the only reagent is reported. The first C-H functionalization of triphenylene is ...explored, and proceeds at the most sterically hindered position. This non-chelate assisted C-H functionalization extends the reactivity profile of Pd/C and provides controlled access to π-extended PAHs, an important aspect of work towards the preparation of nanographenes. Mechanistic studies suggest
formation of catalytically active insoluble nanoparticles, and that the reaction likely proceeds
a Pd(0)/Pd(ii) type reaction manifold.
Neutrophil extracellular traps (NETs) are formed when neutrophils expel their DNA, histones and intracellular proteins into the extracellular space or circulation. NET formation is dependent on ...autophagy and is mediated by citrullination of histones to allow for the unwinding and subsequent expulsion of DNA. NETs have an important role in the pathogenesis of several sterile inflammatory diseases, including malignancy, therefore we investigated the role of NETs in the setting of pancreatic ductal adenocarcinoma (PDA). Neutrophils isolated from two distinct animal models of PDA had an increased propensity to form NETs following stimulation with platelet activating factor (PAF). Serum DNA, a marker of circulating NET formation, was elevated in tumor bearing animals as well as in patients with PDA. Citrullinated histone H3 expression, a marker of NET formation, was observed in pancreatic tumors obtained from murine models and patients with PDA. Inhibition of autophagy with chloroquine or genetic ablation of receptor for advanced glycation end products (RAGE) resulted in decreased propensity for NET formation, decreased serum DNA and decreased citrullinated histone H3 expression in the pancreatic tumor microenvironment. We conclude that NETs are upregulated in pancreatic cancer through RAGE-dependent/autophagy mediated pathways.
To evaluate the accuracy of STOP-Bang (SBQ) questionnaire in the screening of patients with obstructive sleep apnea (OSA).
The data were collected from September, 2011 to May, 2012 at the Sleep ...Medicine Center of West China Hospital, Sichuan University. A total of 350 consecutive patients (302 males and 48 females, 19-68 years old, average (42.9±11.0) years old) with suspected OSA who underwent an overnight polysomnography (PSG) were recruited into this study. SBQ questionnaire was completed. Based on the severity of OSA which were determined by apnea-hypopnea index (AHI), the patients were classified into four groups of primary snoring (<5 events/h), mild (5-14 events/h), moderate (15-29 events/h) and severe OSA (≥30 events/h). To evaluate the accuracy of SBQ, sensitivity, specificity, positive predictive values, negative predictive values and the area under the receiver operating characteristics curve of SBQ questionnaire were calculated.
Of the subjects, 322 (92.0%) were classified as high risk based on th
The recruitment of the actin-regulatory proteins cortactin and profilin-1 (Pfn-1) to the membrane is important for the regulation of actin cytoskeletal reorganization and smooth muscle contraction. ...Polo-like kinase 1 (Plk1) and the type III intermediate filament protein vimentin are involved in smooth muscle contraction. Regulation of complex cytoskeletal signaling is not entirely elucidated. The aim of this study was to evaluate the role of nestin (a type VI intermediate filament protein) in cytoskeletal signaling in airway smooth muscle.
Nestin expression in human airway smooth muscle (HASM) was knocked down by specific shRNA or siRNA. The effects of nestin knockdown (KD) on the recruitment of cortactin and Pfn-1, actin polymerization, myosin light chain (MLC) phosphorylation, and contraction were evaluated by cellular and physiological approaches. Moreover, we assessed the effects of non-phosphorylatable nestin mutant on these biological processes.
Nestin KD reduced the recruitment of cortactin and Pfn-1, actin polymerization, and HASM contraction without affecting MLC phosphorylation. Moreover, contractile stimulation enhanced nestin phosphorylation at Thr-315 and the interaction of nestin with Plk1. Nestin KD also diminished phosphorylation of Plk1 and vimentin. The expression of T315A nestin mutant (alanine substitution at Thr-315) reduced the recruitment of cortactin and Pfn-1, actin polymerization, and HASM contraction without affecting MLC phosphorylation. Furthermore, Plk1 KD diminished nestin phosphorylation at this residue.
Nestin is an essential macromolecule that regulates actin cytoskeletal signaling via Plk1 in smooth muscle. Plk1 and nestin form an activation loop during contractile stimulation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To examine the clinical, genetic, and neuropathologic features of posterior cortical atrophy (PCA).
Using a broad definition of PCA as a syndrome with the insidious onset of visual dysfunction in the ...absence of primary ophthalmologic causes, the authors identified and then reviewed the presenting signs and symptoms, ApoE genotypes, tau haplotypes, and neuropathologic findings when available of PCA cases from two dementia research centers collected over the past 14 years.
The authors identified 40 PCA cases. Their mean age at symptom onset was 60.5 +/- 8.9 years. There were twice as many women as men in the series. The principal types of visual impairment were simultanagnosia (82%) and visual field defect (47.5%). Acalculia, alexia, and anomia were also common. Insight was preserved in almost all (95%) early in the disorder. Neither apoE epsilon4 nor tau haplotype frequencies were different from typical Alzheimer disease (AD). Nine patients had died and underwent postmortem examination. Seven autopsied cases had AD pathology but when compared to typical AD, the neurofibrillary tangle (NFT) densities were significantly higher in Brodmann areas 17 and 18 (p < 0.05) and significantly lower in the hippocampus (p < 0.05). Two cases had corticobasal degeneration with maximal involvement of tau positive glial pathology in the posterior parietal lobe and Brodmann areas 17 and 18.
PCA is a distinctive dementia syndrome in which the most pronounced pathologic involvement is in the occipitoparietal regions independent of the specific underlying pathology. AD was the most common pathologic cause, but its regional distribution differed from typical AD.
Activation of the induced receptor for advanced glycation end products (RAGE) leads to initiation of NF-kappaB and MAP kinase signaling pathways, resulting in propagation and perpetuation of ...inflammation. RAGE-knockout animals are less susceptible to acute inflammation and carcinogen-induced tumor development. We have reported that most forms of tumor cell death result in release of the RAGE ligand, high-mobility group protein 1 (HMGB1). We now report a novel role for RAGE in the tumor cell response to stress. Targeted knockdown of RAGE in the tumor cell, leads to increased apoptosis, diminished autophagy and decreased tumor cell survival . In contrast, overexpression of RAGE is associated with enhanced autophagy, diminished apoptosis and greater tumor cell viability. RAGE limits apoptosis through a p53-dependent mitochondrial pathway. Moreover, RAGE-sustained autophagy is associated with decreased phosphorylation of mammalian target of rapamycin (mTOR) and increased Beclin-1/VPS34 autophagosome formation. These findings show that the inflammatory receptor, RAGE, has a heretofore unrecognized role in the tumor cell response to stress. Furthermore, these studies establish a direct link between inflammatory mediators in the tumor microenvironment and resistance to programmed cell death. Our data suggest that targeted inhibition of RAGE or its ligands may serve as novel targets to enhance current cancer therapies.
The recovery efficiency of aquifer storage systems with radial flow fields are studied for heterogeneous aquifers. Macrodispersion, arising from spatially heterogeneous hydraulic conductivity, is ...modeled as a scale‐dependent mechanical dispersion process. Approximate solutions for the recovery efficiency as a function of local dispersion and macrodispersion parameters, the injection‐extraction rate Q $Q$ and duration T $T$, and storage cycle count, are derived and validated against numerical simulations. If macrodispersion dominates and the macrodispersion coefficient scales linearly with distance, the recovery efficiency is independent of both Q,T $Q,T$. For sublinear and superlinear scalings, recovery increases and decreases respectively if Q,T $Q,T$ increases. However, if local dispersion dominates, increasing Q,T $Q,T$ always increases recovery. As macrodispersion becomes increasingly dominant with scale, the recovery efficiency may be a nonmonotonic function of Q,T $Q,T$, with a maximum. In homogeneous aquifers, nonmonotonicity does not occur for 1D and 2D radial flow, but occurs for 3D radial flow fields only as a function of T $T$, not Q $Q$. These methods may also be used for fitting local dispersion and macrodispersion parameters with push‐pull tests using recovery data, with advantages in scope of applicability and ease of data acquisition and interpretation, compared to existing push‐pull test methods, which fit to breakthrough curves and do not consider macrodispersion. Furthermore, characterizing macrodispersion with push‐pull tests may be advantageous over methods that use observation wells, as observation well placement may be challenging in highly heterogeneous aquifers. The results show that the macrodispersion parameters are not innate aquifer hydraulic properties, as their values vary with flow field geometry.
Key Points
New methods for evaluating heat (ATES) and freshwater (ASR) storage systems, and interpreting push‐pull tests, in heterogeneous aquifers
Approximate solutions for recovery efficiency, where macrodispersion is modeled as a scale‐dependent dispersion process
Depending on the scale‐dependence function, recovery may vary non‐monotonically with stored volume under planar and cylindrical flow
The reliability of chronic, brain‐penetrating electrodes must be improved for these ‐neural recording technologies to be viable in widespread clinical applications. One approach to improving ...electrode reliability is to reduce the foreign body response at the probe‐tissue interface. In this work, silk fibroin is investigated as a candidate material for fabricating mechanically dynamic neural probes with enhanced biocompatibility compared to traditional electrode materials. Silk coatings are applied to flexible cortical electrodes to produce devices that transition from stiff to flexible upon hydration. Theoretical modeling and in vitro testing show that the silk coatings impart mechanical properties sufficient for the electrodes to penetrate brain tissue. Further, it is demonstrated that silk coatings may reduce some markers of gliosis in an in vitro model and that silk can encapsulate and release the gliosis‐modifying enzyme chondroitinase ABC. This work establishes a basis for future in vivo studies of silk‐based brain‐penetrating electrodes, as well as the use of silk materials for other applications in the central nervous system where gliosis must be controlled.
Silk fibroin is investigated as a novel material for fabricating brain‐penetrating electrodes with dynamic mechanical properties and the capacity to deliver sensitive therapeutics. Silk coatings are shown to natively reduce some markers of gliosis in vitro, and a further reduction is demonstrated by encapsulation and release of the enzyme chondroitinase ABC.
The recognition of nucleic acids by the innate immune system during viral infection results in the production of type I interferons and the activation of antiviral immune responses. The RNA helicases ...RIG-I and MDA-5 recognize distinct types of cytosolic RNA species and signal through the mitochondrial protein MAVS to stimulate the phosphorylation and activation of the transcription factors IRF3 and IRF7, thereby inducing type I interferon expression. Alternatively, the activation of NF-kappaB leads to proinflammatory cytokine production. The function of MAVS is dependent on both its C-terminal transmembrane (TM) domain and N-terminal caspase recruitment domain (CARD). The TM domain mediates MAVS dimerization in response to viral RNA, allowing the CARD to bind to and activate the downstream effector TRAF3. Notably, dimerization of the MAVS CARD alone is sufficient to activate IRF3, IRF7, and NF-kappaB. However, TRAF3-deficient cells display only a partial reduction in interferon production in response to RNA virus infection and are not defective in NF-kappaB activation. Here we find that the related ubiquitin ligase TRAF5 is a downstream target of MAVS that mediates both IRF3 and NF-kappaB activation. The TM domain of MAVS allows it to dimerize and thereby associate with TRAF5 and induce its ubiquitination in a CARD-dependent manner. Also, NEMO is recruited to the dimerized MAVS CARD domain in a TRAF3 and TRAF5-dependent manner. Thus, our findings reveal a possible function for TRAF5 in mediating the activation of IRF3 and NF-kappaB downstream of MAVS through the recruitment of NEMO. TRAF5 may be a key molecule in the innate response against viral infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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