A Comprehensive Analysis of the CaMK2A Gene and Susceptibility to Alzheimer’s Disease in the Han Chinese Population

There is ample evidence suggesting that calcium/calmodulin-dependent protein kinase II alpha (CaMK2A) may play an important role in the pathophysiology of Alzheimer’s disease (AD). This genetic study aimed to investigate whether CaMK2A confers susceptibility to the development of AD in the Han Chinese population. A total of seven single nucleotide polymorphisms (SNPs) within CaMK2A were screened in two independent cohorts from southwestern China (333 AD patients and 334 controls) and eastern China (382 AD patients and 426 controls) to discern the potential association between this gene and AD. In addition, a cross-platform normalized expression resource was used to investigate whether CaMK2A is differentially expressed in the brain between individuals with AD and the controls. In addition, expression quantitative trait loci (eQTL) analysis was used to explore the differences in CaMK2A expression in the brain among different genotypes. The cross-platform normalized data showed significant differences in CaMK2A expression in the hippocampus, entorhinal cortex and temporal cortex between the AD patients and the control subjects (|log FC| > 0.1, P < 0.05); however, only the differences in the hippocampus and temporal cortex remained after the multiple comparisons correction [false discovery rate (FDR)-corrected, P < 0.05]. The frequency of the rs4958445 genotype was significantly different between the AD subjects and the controls from southwestern China (P = 0.013, P = 0.034 after FDR correction). When the two samples were combined, rs4958445 still showed a significant association with AD (P = 0.044). Haplotype analysis indicated that the T-A-C-A-T-C-C and T-G-C-A-T-C-C haplotypes in the southwestern cohort and the T-G-C-G-C-T-C haplotype in the eastern cohort, consisting of rs10051644, rs6869634, rs3797617, rs3756577, rs4958445, rs10515639 and rs6881743, showed a significant association with AD (P = 0.037, P = 0.026 and P = 0.045, respectively). Furthermore, the brain eQTL analysis revealed a significant association between the rs4958445 polymorphism and CaMK2A expression in the inferior olivary nucleus (P = 0.029). Our results suggest an important role for CaMK2A in the pathophysiology of AD in the Han Chinese population, especially the southwestern population

Multi-scale material/structure integrated elastic metamaterial for broadband vibration absorbing

To break the high additional mass ratio requirement of traditional vibration absorbing materials/devices, and overcome the shortcoming of the narrow operating frequency band of conventional local resonance metamaterial dampers, this paper proposes a lightweight multi-scale material/structure integrated elastic metamaterial for broadband vibration absorption. By replacing the mass components in the macroscopic metamaterial vibration absorber with a composite mass body filled with microscopic particle materials, a multi-scale structure/material integrated design between the macroscopic oscillator and microscopic particle is realized. The macroscopic oscillator absorbs low-frequency vibration, while the microscopic particle cluster absorbs medium–high frequency vibration, thereby achieving a broadband vibration absorption covering the low-medium–high ranges. Based on the band gap theory and the multiphase flow theory of gas-particle, this paper systematically analyzes the band gap effect of multi-scale metamaterials and the dissipation capacity of medium–high frequency caused by particle damping. The structure exhibits commendable vibration damping performance. The multi-scale integrated vibration damper retains the lightweight and sub-wavelength characteristics of the traditional local resonance unit cells, while greatly broadening the working bandwidth, and having potential applications in low-frequency broadband vibration reduction of various mechanical equipment

Varied hypoxia adaptation patterns of embryonic brain at different development stages between Tibetan and Dwarf laying chickens

Abstract Background Tibetan chickens (Gallus gallus; TBCs), an indigenous breed distributed in the Qinghai-Tibet Plateau, are well adapted to the hypoxic environment. Currently, the molecular genetic basis of hypoxia adaptation in TBCs remains unclear. This study investigated hypoxia adaptation patterns of embryonic brain at different development stages by integrating analysis of the transcriptome with our previously published metabolome data in TBCs and Dwarf Laying Chickens (DLCs), a lowland chicken breed. Results During hypoxia, the results revealed that 1334, 578, and 417 differentially expressed genes (DEGs) (|log2 fold change|>1, p-value < 0.05) on days 8, 12, and 18 of development, respectively between TBCs and DLCs. Gene Ontology (GO) and pathway analyses revealed that DEGs are mainly related to metabolic pathways, vessel development, and immune response under hypoxia. This is consistent with our metabolome data that TBCs have higher energy metabolism than DLCs during hypoxia. Some vital DEGs between TBCs and DLCs, such as EPAS1, VEGFD, FBP1, FBLN5, LDHA, and IL-6 which are involved in the HIF pathway and hypoxia regulation. Conclusion These results suggest varied adaptation patterns between TBCs and DLCs under hypoxia. Our study provides a basis for uncovering the molecular regulation mechanism of hypoxia adaptation in TBCs and a potential application of hypoxia adaptation research for other animals living on the Qinghai-Tibet Plateau, and may even contribute to the study of brain diseases caused by hypoxia

Study of Blast Mitigation Performance and Fracture Mechanism of Polyurea under Contact Explosion

In order to further study the blast mitigation performance of polyurea and to investigate the protection mechanism and damage characteristics of polyurea-protected structures under contact explosion loads, based on earlier work, this paper investigated the response and energy absorption performance of polyurea under various frequency loads. Qtech T26 blast mitigation polyurea (T26 polyurea) was adopted to protect the reinforced concrete (RC) slab and damage analysis of the post-explosion specimens was carried out at micro and macro levels. The response and energy absorption capacity of the material towards different frequency loads were investigated by dynamic mechanical analysis (DMA). Protective performance of T26 polyurea on RC slab was examined with a 10 kg TNT contact explosion test. Scanning electron microscopy (SEM) was employed to analyze the microscopic fracture morphology of the typical areas of the coating after the explosion. The chemical structure changes of the blast-face coating before and after the explosion were compared by Fourier transform infrared spectroscopy (FTIR). The results show that the glass transition region of T26 polyurea is &minus;40 &deg;C to 10 &deg;C, which is a large temperature range, and the microphase separation of T26 polyurea is low. It is significantly influenced by the ambient temperature and loading frequency. The energy absorption of T26 polyurea is realized through the interaction between the hard and soft segments. When the frequency is between 102 Hz and 106 Hz, the loss factor of T26 polyurea is between 0.20 and 0.31, which exhibits a good energy dissipation performance. In the contact explosion of 10 kg TNT, the fragmentation rate of the coated specimen decreased significantly compared with that of the unprotected specimen, realizing the zero fragmentation protection effect on the back-blast face. The maximum deformation area and the main energy absorption area of T26 polyurea under contact explosion is the ring area outside the longitudinal deformation area. The chemical structure of T26 polyurea changed significantly after the explosion; typically the N-H bonds, etc., were broken and the percentage of hydrogen bonding was reduced. T26 polyurea has realized the protection effect of zero fragmentation of large-equivalent contact explosion, which has a high application value for blast mitigation and blast-fragmentation prevention in actual engineering

Effect of Simmering Technology on Components and Activity of <i>Myristica fragrans</i> Houtt.

This study aims to optimize the processing of Myristica fragrans Houtt. by talcum powder simmering using single-factor and orthogonal experimental methods, and the overall desirability values of dehydrodiisoeugenol and essential oils content were selected as indicators of the process. The new process reduced the total content of the three toxic components, namely myristicin, safrole and elemicin, from 1.91% to 1.16% before and after processing, indicating that the toxic components were reduced by 39%. The IC50 of the essential oils before and after processing were 1.002 ± 0.05 and 0.233 ± 0.05 mg/mL for DPPH scavenging activity and 0.132 ± 0.04 and 0.057 ± 0.05 mg/mL for ABTS scavenging activity, respectively. And the absorbance of the antioxidant activity against Ferric reducing power ranged from 0.213 to 0.709 and from 0.225 to 0.755, respectively. The minimum inhibitory concentration for Staphylococcus aureus, Bacillus pumilus and Escherichia coli were all lower after processing than before. The antioxidant activity and antibacterial activity of the essential oils after processing were better than before. The results of the survival of zebrafish embryos at different concentrations of essential oils at 0–168 h post fertilisation were higher after processing than before. These findings suggest that processing plays the role of reducing toxicity and increasing beneficial effects. They provide a scientific basis not only for the processing of M. fragrans, but also for the processing of other foods

Influences of naringin supplementation on ruminal fermentation, inflammatory response, antioxidant capacity and bacterial community in high-concentrate diet of fattening goats

The objective of this study was to evaluate the effects of dietary naringin supplementation on rumen fermentation, inflammatory response and bacterial communities in fattening goats fed high-concentrate diet. Twenty four Boer male goats were randomly divided into three groups and assigned to receive dietary treatments. The three dietary treatments were a normal diet, a high-concentrate diet and a high-concentrate diet supplemented with 500 mg of naringin/kg of dry matter intake. Rumen fluid and plasma samples were collected at the end of the animal trial. Rumen fluid were analysed for pH, short-chain fatty acids, endotoxin (lipopolysaccharide, LPS) and microbiota. Illumina Miseq sequencing of the 16S rRNA gene was applied to investigate ruminal bacterial communities. The concentrations of interleukin −6 and tumour necrosis factor alpha as well as LPS-binding protein, haptoglobin, serum amyloid A and the activities of antioxdant enzymes in plasma were analysed. The result showed that feeding the high concentrate diet shifted the ruminal fermentation pattern from acetate towards propionate and valerate, and improved growth performance compared with the control group. However, the high concentrate diet promoted ruminal pH reduction and LPS release, modified bacterial communities and increased systemic inflammatory response. Naringin supplementation increased molar proportions butyrate and decreased valerate. Naringin supplementation decreased inflammatory response and increased the activities of antioxdant enzymes in plasma. Moreover, naringin addition increased the relative abundance of Bacteroidetes at the phylum level and Rikenellaceae_RC9_gut_group at the genus level. Taken together, these results suggest that dietary supplementation with naringin attenuates high grain diet-induced inflammatory response and modifies ruminal fermentation. HIGHLIGHTS Dietary supplementation of naringin decreased inflammatory response and increased the activities of antioxdant enzymes in fattening goats. Naringin supplementation changed ruminal microbiota of fattening goats. Naringin has potential for use as feed additive to modify ruminal fermentation in a high-grain intensive ruminant production

Biodegradation of Quinoline by a Newly Isolated Salt-Tolerating Bacterium <i>Rhodococcus gordoniae</i> Strain JH145

Quinoline is a typical nitrogen-heterocyclic compound with high toxicity and carcinogenicity which exists ubiquitously in industrial wastewater. In this study, a new quinoline-degrading bacterial strain Rhodococcus sp. JH145 was isolated from oil-contaminated soil. Strain JH145 could grow with quinoline as the sole carbon source. The optimum growth temperature, pH, and salt concentration were 30 °C, 8.0, and 1%, respectively. 100 mg/L quinoline could be completely removed within 28 h. Particularly, strain JH145 showed excellent quinoline biodegradation ability under a high-salt concentration of 7.5%. Two different quinoline degradation pathways, a typical 8-hydroxycoumarin pathway, and a unique anthranilate pathway were proposed based on the intermediates identified by liquid chromatography–time of flight mass spectrometry. Our present results provided new candidates for industrial application in quinoline-contaminated wastewater treatment even under high-salt conditions