Environmental Enrichment Enhances Cav 2.1 Channel-Mediated Presynaptic Plasticity in Hypoxic–Ischemic Encephalopathy

Hypoxic–ischemic encephalopathy (HIE) is a devastating neonatal brain condition caused by lack of oxygen and limited blood flow. Environmental enrichment (EE) is a classic paradigm with a complex stimulation of physical, cognitive, and social components. EE can exert neuroplasticity and neuroprotective effects in immature brains. However, the exact mechanism of EE on the chronic condition of HIE remains unclear. HIE was induced by a permanent ligation of the right carotid artery, followed by an 8% O₂ hypoxic condition for 1 h. At 6 weeks of age, HIE mice were randomly assigned to either standard cages or EE cages. In the behavioral assessments, EE mice showed significantly improved motor performances in rotarod tests, ladder walking tests, and hanging wire tests, compared with HIE control mice. EE mice also significantly enhanced cognitive performances in Y-maze tests. Particularly, EE mice showed a significant increase in Ca_v 2.1 (P/Q type) and presynaptic proteins by molecular assessments, and a significant increase of Ca_v 2.1 in histological assessments of the cerebral cortex and hippocampus. These results indicate that EE can upregulate the expression of the Ca_v 2.1 channel and presynaptic proteins related to the synaptic vesicle cycle and neurotransmitter release, which may be responsible for motor and cognitive improvements in HIE.     

Investigation of non-isothermal crystallization,dynamic mechanical and dielectric properties of poly(ether-ketone) matrix composites

ABSTRACT

Poly(ether-ketone)/hexagonal boron nitride (h-BN) composites reinforced with micrometer-sized h-BN particles were investigated. The composites exhibited glass transition temperature (T_g) and thermal stability over 160°C and 560°C, respectively. The melting point and peak crystallization temperatures of the composites decreased up to 17°C and 12°C, respectively. The linear CTE of the composites decreased both below and above the T_g. The storage modulus increased with increasing h-BN content at all temperatures (50–250°C). The composites possessed excellent dielectric properties with insignificant dispersion with increasing frequency. Thus, resultant composites are promising candidates for the printed circuit boards/electronic substrates.     

Inhibition of Soluble Epoxide Hydrolase Ameliorates Phenotype and Cognitive Abilities in a Murine Model of Niemann Pick Type C Disease

Niemann–Pick type C (NPC) disease is a rare autosomal recessive inherited childhood neurodegenerative disease characterized by the accumulation of cholesterol and glycosphingolipids, involving the autophagy-lysosome system. Inhibition of soluble epoxide hydrolase (sEH), an enzyme that metabolizes epoxy fatty acids (EpFAs) to 12-diols, exerts beneficial effects in modulating inflammation and autophagy, critical features of the NPC disease. This study aims to evaluate the effects of UB-EV-52, an sEH inhibitor (sEHi), in an NPC mouse model (Npc) by administering it for 4 weeks (5 mg/kg/day). Behavioral and cognitive tests (open-field test (OF)), elevated plus maze (EPM), novel object recognition test (NORT) and object location test (OLT) demonstrated that the treatment produced an improvement in short- and long-term memory as well as in spatial memory. Furthermore, UB-EV-52 treatment increased body weight and lifespan by 25% and reduced gene expression of the inflammatory markers (i.e., Il-1β and Mcp1) and enhanced oxidative stress (OS) markers (iNOS and Hmox1) in the treated Npc mice group. As for autophagic markers, surprisingly, we found significantly reduced levels of LC3B-II/LC3B-I ratio and significantly reduced brain protein levels of lysosomal-associated membrane protein-1 (LAMP-1) in treated Npc mice group compared to untreated ones in hippocampal tissue. Lipid profile analysis showed a significant reduction of lipid storage in the liver and some slight changes in homogenated brain tissue in the treated NPC mice compared to the untreated groups. Therefore, our results suggest that pharmacological inhibition of sEH ameliorates most of the characteristic features of NPC mice, demonstrating that sEH can be considered a potential therapeutic target for this disease.     

The Bark Beetle Dendroctonus rhizophagus (Curculionidae: Scolytinae) Has Digestive Capacity to Degrade Complex Substrates: Functional Characterization and Heterologous Expression of an α-Amylase

Dendroctonus-bark beetles are natural agents contributing to vital processes in coniferous forests, such as regeneration, succession, and material recycling, as they colonize and kill damaged, stressed, or old pine trees. These beetles spend most of their life cycle under stem and roots bark where they breed, develop, and feed on phloem. This tissue is rich in essential nutrients and complex molecules such as starch, cellulose, hemicellulose, and lignin, which apparently are not available for these beetles. We evaluated the digestive capacity of Dendroctonus rhizophagus to hydrolyze starch. Our aim was to identify α-amylases and characterize them both molecularly and biochemically. The findings showed that D. rhizophagus has an α-amylase gene (AmyDr) with a single isoform, and ORF of 1452 bp encoding a 483-amino acid protein (53.15 kDa) with a predicted signal peptide of 16 amino acids. AmyDr has a mutation in the chlorine-binding site, present in other phytophagous insects and in a marine bacterium. Docking analysis showed that AmyDr presents a higher binding affinity to amylopectin compared to amylose, and an affinity binding equally stable to calcium, chlorine, and nitrate ions. AmyDr native protein showed amylolytic activity in the head-pronotum and gut, and its recombinant protein, a polypeptide of ~53 kDa, showed conformational stability, and its activity is maintained both in the presence and absence of chlorine and nitrate ions. The AmyDr gene showed a differential expression significantly higher in the gut than the head-pronotum, indicating that starch hydrolysis occurs mainly in the midgut. An overview of the AmyDr gene expression suggests that the amylolytic activity is regulated through the developmental stages of this bark beetle and associated with starch availability in the host tree.     

Diffusion Magnetic Resonance Imaging-Based Biomarkers for Neurodegenerative Diseases

There has been an increasing prevalence of neurodegenerative diseases with the rapid increase in aging societies worldwide. Biomarkers that can be used to detect pathological changes before the development of severe neuronal loss and consequently facilitate early intervention with disease-modifying therapeutic modalities are therefore urgently needed. Diffusion magnetic resonance imaging (MRI) is a promising tool that can be used to infer microstructural characteristics of the brain, such as microstructural integrity and complexity, as well as axonal density, order, and myelination, through the utilization of water molecules that are diffused within the tissue, with displacement at the micron scale. Diffusion tensor imaging is the most commonly used diffusion MRI technique to assess the pathophysiology of neurodegenerative diseases. However, diffusion tensor imaging has several limitations, and new technologies, including neurite orientation dispersion and density imaging, diffusion kurtosis imaging, and free-water imaging, have been recently developed as approaches to overcome these constraints. This review provides an overview of these technologies and their potential as biomarkers for the early diagnosis and disease progression of major neurodegenerative diseases.     

基于XGBoost算法的垃圾短信分层分级治理体系

为有效整治垃圾短信,不断提升不良信息治理的精准性,文章基于XGBoost算法构建了一套科学的分层分级垃圾短信治理体系。通过对用户入网、消费、通信行为等特征进行建模与运算,识别出用户发送垃圾短信的风险系数,并定义了六级用户。分级名单生成后,依托于垃圾短信拦截系统的分级策略管理功能,分别设置相匹配的拦截策略。在加大对中高危用户的识别和拦截力度的同时,有效降低了高价值用户因不良信息治理导致被误拦截的风险。该治理体系应用于辽宁移动管理实际以来,垃圾短信平均投诉量降幅34.82%。误关停投诉率稳定在0.1%以内。一至三级高价值客户群关停投诉量降幅27.43%。     

Thermal and dynamic mechanical behavior of epoxy composites reinforced with post-consumed yerba mate

Yerba mate (YM) is widely consumed in Latin American countries, and its residues can be used as bio-resources such as reinforced in epoxy composites. The present work aims to produce epoxy resin composites and evaluate the influence of post-consumed YM as reinforcement. The concentrations of YM used were 5, 10, and 20% (wt/wt). Chemical, thermal, morphological, and dynamic mechanical behaviors were explored. The YM incorporation did not influence chemically on the epoxy structure and a pull-out phenomenon was observed as YM content increased. The YM at lower concentrations (5 and 10%) led to higher values of activation energies calculated from model-free isoconversional methods. On the other hand, the composite e/YM 20 wt% improved all dynamic-mechanical properties. YM proved to be a suitable and cheap reinforcement for epoxy resin.     

Wear and thermal behavior of basalt fiber reinforced rice husk/polyvinyl chloride composites

Plant fiber reinforced polymer composites (PFRPs) in practical application are often subjected to both complex friction and variable temperature environments. The present work explores the possibility of reinforcing rice husk/polyvinyl chloride (RH/PVC) composites with basalt fibers (BF) for developing a new wear resistant material with improved thermal stability. The results showed that the structural strength and wear resistance of the composites increased at first and then decreased with an increasing ratio of BF/RH, the highest value occurred at a BF/RH ratio of 8/42. The thermal stability of composites had a positive relationship with BF/RH ratio. The composites added with BF all possessed improved performance in comparison with unadded composites. Hence, the findings of this article proposed some new perspectives on improving the wear resistance and thermal stability of PFRPs that would broaden their practical application.     

Ordinary Gasoline Emissions Induce a Toxic Response in Bronchial Cells Grown at Air-Liquid Interface

Gasoline engine emissions have been classified as possibly carcinogenic to humans and represent a significant health risk. In this study, we used MucilAir™, a three-dimensional (3D) model of the human airway, and BEAS-2B, cells originating from the human bronchial epithelium, grown at the air-liquid interface to assess the toxicity of ordinary gasoline exhaust produced by a direct injection spark ignition engine. The transepithelial electrical resistance (TEER), production of mucin, and lactate dehydrogenase (LDH) and adenylate kinase (AK) activities were analyzed after one day and five days of exposure. The induction of double-stranded DNA breaks was measured by the detection of histone H2AX phosphorylation. Next-generation sequencing was used to analyze the modulation of expression of the relevant 370 genes. The exposure to gasoline emissions affected the integrity, as well as LDH and AK leakage in the 3D model, particularly after longer exposure periods. Mucin production was mostly decreased with the exception of longer BEAS-2B treatment, for which a significant increase was detected. DNA damage was detected after five days of exposure in the 3D model, but not in BEAS-2B cells. The expression of CYP1A1 and GSTA3 was modulated in MucilAir™ tissues after 5 days of treatment. In BEAS-2B cells, the expression of 39 mRNAs was affected after short exposure, most of them were upregulated. The five days of exposure modulated the expression of 11 genes in this cell line. In conclusion, the ordinary gasoline emissions induced a toxic response in MucilAir™. In BEAS-2B cells, the biological response was less pronounced, mostly limited to gene expression changes.