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Taurine (Tau) has many profound physiological functions, but its role and molecular mechanism in muscle cells are still not fully understood. In this study, we investigated the role and underlying molecular mechanism of Tau on protein synthesis and proliferation of C2C12 myoblast cells. Cells were treated with Tau (0, 60, 120, 180 and 240 μM) for 24 h. Tau dose-dependently promoted protein synthesis, cell proliferation, mechanistic target of rapamycin protein (mTOR) phosphorylation and also AT-rich interaction domain 4B (ARID4B) expression, with the best stimulatory effects at 120 μM. LY 294002 treatment showed that Tau promoted ARID4B expression in a phosphoinositide 3-kinase (PI3K)-dependent manner. ARID4B knockdown (by small interfering RNA transfection for 24 h) prevented Tau from stimulating protein synthesis and cell proliferation, whereas ARID4B gene activation (using the CRISPR/dCas9 technology) had stimulatory effects. ARID4B knockdown abolished Tau signalling to mRNA expression and protein phosphorylation of mTOR, whereas ARID4B gene activation had stimulatory effects. Chromatin immunoprecipitation (ChIP)-PCR identified that all of ARID4B, H3K27ac and H3K27me3 bound to the −4368 to –4591 bp site in the mTOR promoter, and ChIP-quantitative PCR (qPCR) further detected that Tau stimulated ARID4B binding to this site. ARID4B knockdown or gene activation did not affect H3K27me3 binding to the mTOR promoter but decreased or increased H3K27ac binding, respectively. Furthermore, ARID4B knockdown abolished the stimulation of Tau on H3K27ac binding to the mTOR promoter. In summary, these data uncover that Tau promotes protein synthesis and proliferation of C2C12 myoblast cells through the PI3K-ARID4B-mTOR pathway, providing a deep understanding of how Tau regulates anabolism in muscle cells.
The aim of our study was to determine the distribution of hepatitis B virus (HBV) genotypes and subgenotypes in ethnic minorities in Yunnan province to provide evidence supporting the theoretical basis for hepatitis B prevention and control. We obtained serum samples and demographic data from 765 individuals reported by Yunnan province who had either acute or chronic HBV infection and were from one of 20 ethnic minority populations: Achang, Bai, Brown, Tibetan, Dai, Deang, Dulong, Hani, Hui, Jingpo, Lahu, Yi, Lisu Miao, Naxi, Nu, Pumi, Wa, Yao, or Zhuang people. We sequenced the HBV DNA and determined the genotypes and subgenotypes of the isolated HBVs. We mapped the genotype and subgenotype distribution by ethnic minority population and conducted descriptive analyses. There were four genotypes among the 20 ethnic groups: genotype B (21.3% of samples), C (76.6%), D (1.8%) and I (0.3%). The most common subgenotype was C1. There were no genotype differences by gender (P = 0.954) or age (P = 0.274), but there were differences by region (P < 0.001). There were differences in genotype distribution (P < 0.001) and subgenotype distribution (P = 0.011) by ethnic group. Genotype D was most prominent in Tibet and most HBV isolates were C/D recombinant viruses. The only two genotype I virus isolates were in Zhuang people. Susceptibility and geographic patterns may influence HBV prevalence in different ethnic populations, but additional research is needed for such a determination.
Intestinal atresia (IA), a common cause of neonatal intestinal obstruction, is a developmental defect, which disrupts the luminal continuity of the intestine. Here, we investigated (i) the process of lumen formation in human embryos; and (ii) how a defective lumen formation led to IA. We performed histological and histochemical study on 6–10 gestation week human embryos and on IA septal regions. To investigate the topology of embryonic intestine development, we conducted 3D reconstruction. We showed that a 6–7th gestation week embryonic gut has no lumen, but filled with mesenchyme cells and vacuoles of a monolayer of epithelial cells. A narrow gut lumen was formed by gestation week-9, the gut was filled with numerous vacuoles of different sizes, some vacuoles were merging with the developing embryonic gut wall. At gestation week-10, a prominent lumen was developed, only few vacuoles were present and were merging with the intestine wall. At IA septal regions, vacuoles were located in the submucous layer, covered by a single layer of epithelium without glandular structure, and surrounded with fibrous tissue. The mucosal epithelium was developed with lamina propria and basement membrane, but the submucosa and the longitudinal smooth muscle layers were not properly developed. Hence, the vacuoles in IA septum could represent a remnant of vacuoles of embryonic gut. In conclusion, the fusion of vacuoles with the developing intestine wall associates with the disappearance of vacuoles and gut lumen formation in human embryos, and perturbation of these developmental events could lead to IA.
Steam jet milling was applied for the first time to ultra-fine grind the filter cake (moisture content 23.80%) produced by a kaolin concentrator. The material was dehydrated and dried simultaneously during grinding, and the final ground sample met the moisture content requirement for powder products of <2%. The particle size of the ground kaolin samples decreased and the particle-size distribution was more concentrated, indicating that the steam jet milling was more effective for kaolin processing than the conventional dry grinding process. In addition, steam jet milling can improve the whiteness and decrease the crystal order of the samples, thus improving the kaolin properties in follow-up applications.
Beryl from Xuebaoding, Sichuan Province, western China is known for its unusual tabular habit and W–Sn–Be paragenesis in a greisen-type deposit. The crystals are typically colourless transparent to pale blue, often with screw dislocations of hexagonal symmetry on the (0001) crystal faces. Combining electron microprobe analyses and laser ablation inductively coupled plasma mass spectrometry with single-crystal X-ray diffraction (XRD), correlated with Raman and micro-infrared (IR) spectroscopy and imaging, the crystal chemical characteristics are determined. The contents of Na+ (0.24–0.38 atoms per formula unit (apfu)) and Li+ up to 0.38 apfu are at the high end compared to beryl from other localities worldwide. Li+ substitution for Be2+ on the tetrahedral (T2) site is predominantly charge balanced by Na+ on the smaller channel (C2) site, with Na+ ranging from 91.5% to 99.7% (apfu) of the sum of all other alkali elements. Cs+ and minor Rb+ and K+ primarily charge balance the minor M2+ substitution for Al3+ at the A site; all iron at the A site is suggested to be trivalent. The a axis ranges from 9.2161(2) to 9.2171(4) Å, with unit-cell volume from 678.03(3) to 678.48(7) Å3. The c/a ratio of 1.0002–1.0005 is characteristic for T2-type beryl with unit-cell parameters controlled primarily by Be2+ substitution. Transmission micro-IR vibrational spectroscopy and imaging identifies coordination of one or two water molecules to Na+ (type IIs and type IId, respectively) as well as alkali free water (type I). Based on IR absorption cross section and XRD a C1 site water content of 0.4–0.5 apfu is derived, i.e. close to 50% site occupancy. Secondary crystal phases with a decrease in Fe and Mg, yet increase in Na, suggest early crystallisation of aquamarine, with goshenite being late. With similar crystal chemistry to beryl of columnar habit from other localities worldwide, the tabular habit of Xuebaoding beryl seems to be unrelated to chemical composition and alkali content.
Mode distortion induced by stimulated Raman scattering (SRS) has become a new obstacle for the further development of high-power fiber lasers with high beam quality. Here, an approach for effective suppression of the SRS-induced mode distortion in high-power fiber amplifiers has been demonstrated experimentally by adjusting the seed power (output power of seed source) and forward feedback coefficient of the rear port in the seed source. It is shown that the threshold power of the SRS-induced mode distortion can be increased significantly by reducing the seed power or the forward feedback coefficient. Moreover, it has also been found that the threshold power is extremely sensitive to the forward feedback power value from the rear port. The influence of the seed power on the threshold power can be attributed to the fact that the seed power plays an important role in the effective length of the gain fiber in the amplifier. The influence of the forward feedback coefficient on the threshold power can be attributed to the enhanced SRS configuration because the end surface of the rear port together with the fiber in the amplifier constitutes a half-opening cavity. This suppression approach will be very helpful to further develop the high-power fiber amplifiers with high beam quality.
Grain refinement has been applied to enhance the materials strength for miniaturization and lightweight design of nuclear equipment. It is critically important to investigate the low-cycle fatigue (LCF) properties of grain refined 316LN austenitic stainless steels for structural design and safety assessment. In the present work, a series of fine-grained (FG) 316LN steels were produced by thermo-mechanical processes. The LCF properties were studied under a fully reversed strain-controlled mode at room temperature. Results show that FG 316LN steels demonstrate good balance of high strength and high ductility. However, a slight loss of ductility in FG 316LN steel induces a significant deterioration of LCF life. The rapid energy dissipation in FG 316LN steels leads to the reduction of their LCF life. Dislocations develop rapidly in the first stage of cycles, which induces the initial cyclic hardening. The dislocations rearrange to form dislocations cell structure resulting in cyclic softening in the subsequent cyclic deformation. Strain-induced martensite transformation appears in FG 316LN stainless steels at high strain amplitude (Δε/2 = 0.8%), which leads to the secondary cyclic hardening. Moreover, a modified LCF life prediction model for grain refined metals predicts the LCF life of FG 316LN steels well.
A continuous survey on influenza was conducted in Hulunbuir, China from January 2010 to May 2019 to reveal epidemiological, microbiological and air pollutants associated with laboratory-confirmed influenza cases.
Influenza-like illness and severe acute respiratory infection subjects were enrolled from a sentinel hospital in Hulunbuir during the study period for epidemiological and virological investigation. The association between air pollutants and influenza-positivity rate was assessed by a generalised additive model.
Of 4667 specimens, 550 (11.8%) were tested positive for influenza. The influenza-positivity was highest in the age groups of 5–14 years, 50–69 years and ⩾70 years. We found that the effect of particulate matter ⩽2.5 μm (PM2.5) concentrations on the influenza-positivity rate was statistically significant, particularly on day lag-4 and lag-5. Genetic characterisations showed that (H1N1) pdm09 strains belonged to subclade 6B.1 and that influenza B isolates belonged to subclade 1A-3Del, with significant substitutions in the haemagglutinin and neuraminidase proteins compared with those in the WHO-recommended vaccine strains.
Elderly individuals and school-age children were at high risk for influenza infection. PM2.5 concentrations showed significant effects on influenza-positivity rate in Hulunbuir, which could be considered in local influenza prevention strategies.
We investigated the adoption of World Health Organization (WHO) naming of COVID-19 into the respective languages among the Group of Twenty (G20) countries, and the variation of COVID-19 naming in the Chinese language across different health authorities. On May 7, 2020, we identified the websites of the national health authorities of the G20 countries to identify naming of COVID-19 in their respective languages, and the websites of the health authorities in mainland China, Hong Kong, Macau, Taiwan and Singapore and identify their Chinese name for COVID-19. Among the G20 nations, Argentina, China, Italy, Japan, Mexico, Saudi Arabia and Turkey do not use the literal translation of COVID-19 in their official language(s) to refer to COVID-19, as they retain “novel” in the naming of this disease. China is the only G20 nation that names COVID-19 a pneumonia. Among Chinese-speaking jurisdictions, Hong Kong and Singapore governments follow the WHO’s recommendation and adopt the literal translation of COVID-19 in Chinese. In contrast, mainland China, Macau, and Taiwan refer to COVID-19 as a type of pneumonia in Chinese. We urge health authorities worldwide to adopt naming in their native languages that are consistent with WHO’s naming of COVID-19.
Nutritional therapy is a cornerstone of burns management. The optimal macronutrient intake for wound healing after burn injury has not been identified, although high-energy, high-protein diets are favoured. The present study aimed to identify the optimal macronutrient intake for burn wound healing. The geometric framework (GF) was used to analyse wound healing after a 10 % total body surface area contact burn in mice ad libitum fed one of the eleven high-energy diets, varying in macronutrient composition with protein (P5−60 %), carbohydrate (C20−75 %) and fat (F20−75 %). In the GF study, the optimal ratio for wound healing was identified as a moderate-protein, high-carbohydrate diet with a protein:carbohydrate:fat (P:C:F) ratio of 1:4:2. High carbohydrate intake was associated with lower mortality, improved body weight and a beneficial pattern of body fat reserves. Protein intake was essential to prevent weight loss and mortality, but a protein intake target of about 7 kJ/d (about 15 % of energy intake) was identified, above which no further benefit was gained. High protein intake was associated with delayed wound healing and increased liver and spleen weight. As the GF study demonstrated that an initial very high protein intake prevented mortality, a very high-protein, moderate-carbohydrate diet (P40:C42:F18) was specifically designed. The dynamic diet study was also designed to combine and validate the benefits of an initial very high protein intake for mortality, and subsequent moderate protein, high carbohydrate intake for optimal wound healing. The dynamic feeding experiment showed switching from an initial very high-protein diet to the optimal moderate-protein, high-carbohydrate diet accelerated wound healing whilst preventing mortality and liver enlargement.
This paper provides an up-to-date review of the problems related to the generation, detection and mitigation of strong electromagnetic pulses created in the interaction of high-power, high-energy laser pulses with different types of solid targets. It includes new experimental data obtained independently at several international laboratories. The mechanisms of electromagnetic field generation are analyzed and considered as a function of the intensity and the spectral range of emissions they produce. The major emphasis is put on the GHz frequency domain, which is the most damaging for electronics and may have important applications. The physics of electromagnetic emissions in other spectral domains, in particular THz and MHz, is also discussed. The theoretical models and numerical simulations are compared with the results of experimental measurements, with special attention to the methodology of measurements and complementary diagnostics. Understanding the underlying physical processes is the basis for developing techniques to mitigate the electromagnetic threat and to harness electromagnetic emissions, which may have promising applications.
l-Carnitine is essential for mitochondrial β-oxidation and has been used as a lipid-lowering feed additive in humans and farmed animals. d-Carnitine is an optical isomer of l-carnitine and dl-carnitine has been widely used in animal feeds. However, the functional differences between l- and d-carnitine are difficult to study because of the endogenous l-carnitine background. In the present study, we developed a low-carnitine Nile tilapia model by treating fish with a carnitine synthesis inhibitor, and used this model to investigate the functional differences between l- and d-carnitine in nutrient metabolism in fish. l- or d-carnitine (0·4 g/kg diet) was fed to the low-carnitine tilapia for 6 weeks. l-Carnitine feeding increased the acyl-carnitine concentration from 3522 to 10 822 ng/g and alleviated the lipid deposition from 15·89 to 11·97 % in the liver of low-carnitine tilapia. However, as compared with l-carnitine group, d-carnitine feeding reduced the acyl-carnitine concentration from 10 822 to 5482 ng/g, and increased lipid deposition from 11·97 to 20·21 % and the mRNA expression of the genes involved in β-oxidation and detoxification in the liver. d-Carnitine feeding also induced hepatic inflammation, oxidative stress and apoptosis. A metabolomic investigation further showed that d-carnitine feeding increased glycolysis, protein metabolism and activity of the tricarboxylic acid cycle and oxidative phosphorylation. Thus, l-carnitine can be physiologically utilised in fish, whereas d-carnitine is metabolised as a xenobiotic and induces lipotoxicity. d-Carnitine-fed fish demonstrates increases in peroxisomal β-oxidation, glycolysis and amino acid degradation to maintain energy homeostasis. Therefore, d-carnitine is not recommended for use in farmed animals.
Whether borderline personality disorder (BPD) and bipolar disorder are the same or different disorders lacks consistency.
To detect whether grey matter volume (GMV) and grey matter density (GMD) alterations show any similarities or differences between BPD and bipolar disorder.
Web-based publication databases were searched to conduct a meta-analysis of all voxel-based studies that compared BPD or bipolar disorder with healthy controls. We included 13 BPD studies (395 patients with BPD and 415 healthy controls) and 47 bipolar disorder studies (2111 patients with bipolar disorder and 3261 healthy controls). Peak coordinates from clusters with significant group differences were extracted. Effect-size signed differential mapping meta-analysis was performed to analyse peak coordinates of clusters and thresholds (P < 0.005, uncorrected). Conjunction analyses identified regions in which disorders showed common patterns of volumetric alteration. Correlation analyses were also performed.
Patients with BPD showed decreased GMV and GMD in the bilateral medial prefrontal cortex network (mPFC), bilateral amygdala and right parahippocampal gyrus; patients with bipolar disorder showed decreased GMV and GMD in the bilateral medial orbital frontal cortex (mOFC), right insula and right thalamus, and increased GMV and GMD in the right putamen. Multi-modal analysis indicated smaller volumes in both disorders in clusters in the right medial orbital frontal cortex. Decreased bilateral mPFC in BPD was partly mediated by patient age. Increased GMV and GMD of the right putamen was positively correlated with Young Mania Rating Scale scores in bipolar disorder.
Our results show different patterns of GMV and GMD alteration and do not support the hypothesis that bipolar disorder and BPD are on the same affective spectrum.
Nanocrystalline and nanolaminated materials show enhanced radiation tolerance compared with their coarse-grained counterparts, since grain boundaries and layer interfaces act as effective defect sinks. Although the effects of layer interface and layer thickness on radiation tolerance of crystalline nanolaminates have been systematically studied, radiation response of crystalline/amorphous nanolaminates is rarely investigated. In this study, we show that irradiation can lead to formation of nanocrystals and nanotwins in amorphous CuNb layers in Cu/amorphous-CuNb nanolaminates. Substantial element segregation is observed in amorphous CuNb layers after irradiation. In Cu layers, both stationary and migrating grain boundaries effectively interact with defects. Furthermore, there is a clear size effect on irradiation-induced crystallization and grain coarsening. In situ studies also show that crystalline/amorphous interfaces can effectively absorb defects without drastic microstructural change, and defect absorption by grain boundary and crystalline/amorphous interface is compared and discussed. Our results show that tailoring layer thickness can enhance radiation tolerance of crystalline/amorphous nanolaminates and can provide insights for constructing crystalline/amorphous nanolaminates under radiation environment.
Dairy cows with ketosis display severe oxidative stress as well as high blood concentrations of non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHB). Cytochrome P4502E1 (CYP2E1) plays an important role in the induction of oxidative stress. The aim of this study was to investigate CYP2E1 expression and activity in the liver of clinically ketotic cows (in vivo) and the effects of NEFA and BHB on CYP2E1 expression and activity in hepatocytes (in vitro). Dairy cows with clinical ketosis exhibited a low blood concentration of glucose but high concentrations of NEFA and BHB. Hepatic mRNA, protein expression, and activity of CYP2E1 were significantly higher in cows with clinical ketosis than in control cows. In vitro, both NEFA and BHB treatment markedly up-regulated the mRNA and protein expressions as well as activity of CYP2E1 in cow hepatocytes. Taken together, these results indicate that high levels of NEFA and BHB significantly up-regulate the expression and activity of hepatic CYP2E1, and may be influential in the induction of oxidative stress in cows with clinical ketosis.
Serrated flow is one important characteristic of shear bands through which metallic glasses (MGs) accommodate plastic deformation. Serrated flow can be affected by intrinsic properties such as elastic modulus or extrinsic variables such as strain rate. However, the influences of pre-deformation and interfaces on serrated flow are less well understood. In this study, by using in situ micropillar compression inside a scanning electron microscope, we show that pre-deformation (consisting of cyclic loading/unloading below the nominal elastic limit) suppresses serrated flows in amorphous-CuNb but enhances serrated flows in amorphous-CuZr at both high and low strain rates. Moreover, layer interfaces in Cu/amorphous-CuNb multilayers mitigate serrated flows, and the average stress drop and strain duration associated with shear banding process can be tailored. Strain accommodation and energy dissipation via shear banding have clear impact on serrated flows. This study provides new perspectives on tailoring serrated flows and enhancing plastic deformation of MGs.
AlMg alloys have widespread industrial applications. Grain refinement techniques have been frequently used to achieve high strength in these alloys. Here, we report on the fabrication of epitaxial co-sputtered AlMg thin films with high-density growth twins. The microstructure evolution with varying Mg composition has been characterized. Nanoindentation and in-situ micropillar compression tests show that the strength of AlMg alloys increases with increasing Mg composition. The flow stress of epitaxial nanotwinned Al–10 at.% Mg thin film exceeds 800 MPa. The modified Hall–Petch plots incorporating the solid solution strengthening effect suggest that, compared to high angle grain boundaries, incoherent twin boundaries are equivalent barriers to the transmission of dislocations in nanotwinned AlMg alloys.
Familial monozygotic (MZ) twinning reports are rare around the world, and we report a four-generation pedigree with seven recorded pairs of female MZ twins. Whole-genome sequencing of seven family members was performed to explore the featured genetic factors in MZ twins. For variations specific to MZ twins, five novel variants were observed in the X chromosome. These candidates were used to explain the seemingly X-linked dominant inheritance pattern, and only one variant was exonic, located at the 5′UTR region of ZCCHC12 (chrX: 117958597, G > A). Besides, consistent mitochondrial DNA composition in the maternal linage precluded roles of mitochondria for this trait. In this pedigree, autosomes also contain diverse variations specific to MZ twins. Pathway analysis revealed a significant enrichment of genes carrying novel SNVs in the epithelial adherens junction-signaling pathway (p = .011), contributed by FGFR1, TUBB6, and MYH7B. Meanwhile, TBC1D22A, TRIOBP, and TUBB6, also carrying similar SNVs, were involved in the GTPase family-mediated signal pathway. Furthermore, gene-set enrichment analysis for 533 genes covered by copy number variations specific to MZ twins illustrated that the tight junction-signaling pathway was significantly enriched (p < .001). Therefore, the novel changes in the X chromosome and the provided candidate variants across autosomes may be responsible for MZ twinning, giving clues to increase our understanding about the underlying mechanism.
We analyzed research themes in the field of disaster medicine in China to provide references for researchers to understand the research status and developing trends of this field.
Published journal articles were retrieved. A social network analysis was conducted to visualize the relations of high-frequency key words. A cluster analysis was used to classify key words. A strategic diagram analysis was conducted to visualize clusters across the entire research field.
We retrieved 3,079 articles, from which 1,749 articles and 8,284 key words were identified after screening. High-frequency key words were classified into 6 clusters. “Medical rescue” had the highest degree and betweenness centralities. Cluster 4 was located in Quadrant I of the strategic diagrams.
“Medical rescue” is the core key word, and it serves a pivotal “bridge” function. “Emergencies” and similar terms are key words with special statuses. “Natural disaster medical rescue” and “fundamental theories of disaster medicine” constitute the primary and secondary core themes, respectively. “On-site emergency treatment techniques” is a marginalized theme. The other themes are emerging themes that offer considerable scope for future development. Generally, the scope and depth of investigations in this field should be improved. (Disaster Med Public Health Preparedness. 2019;13:405-409)