18 research outputs found

    Vitamin D and cause-specific vascular disease and mortality:a Mendelian randomisation study involving 99,012 Chinese and 106,911 European adults

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    Atomistic Investigation of Titanium Carbide Ti8C5 under Impact Loading

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    Titanium carbides attract attention from both academic and industry fields because of their intriguing mechanical properties and proven potential as appealing candidates in the variety of fields such as nanomechanics, nanoelectronics, energy storage and oil/water separation devices. A recent study revealed that the presence of Ti8C5 not only improves the impact strength of composites as coatings, but also possesses significant strengthening performance as an interlayer material in composites by forming strong bonding between different matrices, which sheds light on the design of impact protection composite materials. To further investigate the impact resistance and strengthening mechanism of Ti8C5, a pilot Molecular Dynamics (MD) study utilizing comb3 potential is carried out on a Ti8C5 nanosheet by subjecting it to hypervelocity impacts. The deformation behaviour of Ti8C5 and the related impact resist mechanisms are assessed in this research. At a low impact velocity ~0.5 km/s, the main resonance frequency of Ti8C5 is 11.9 GHz and its low Q factor (111.9) indicates a decent energy damping capability, which would eliminate the received energy in an interfacial reflection process and weaken the shock waves for Ti8C5 strengthened composites. As the impact velocity increases above the threshold of 1.8 km/s, Ti8C5 demonstrates brittle behaviour, which is signified by its insignificant out-of-plane deformation prior to crack initiation. When tracking atomic Von Mises stress distribution, the elastic wave propagation velocity of Ti8C5 is calculated to be 5.34 and 5.90 km/s for X and Y directions, respectively. These figures are inferior compared with graphene and copper, which indicate slower energy delocalization rates and thus less energy dissipation via deformation is expected prior to bond break. However, because of its relatively small mass density comparing with copper, Ti8C5 presents superior specific penetration. This study provides a fundamental understanding of the deformation and penetration mechanisms of titanium carbide nanosheets under impact, which is crucial in order to facilitate emerging impact protection applications for titanium carbide-related composites.</p

    Atomistic Investigation of Titanium Carbide Ti8C5 under Impact Loading

    No full text
    Titanium carbides attract attention from both academic and industry fields because of their intriguing mechanical properties and proven potential as appealing candidates in the variety of fields such as nanomechanics, nanoelectronics, energy storage and oil/water separation devices. A recent study revealed that the presence of Ti8C5 not only improves the impact strength of composites as coatings, but also possesses significant strengthening performance as an interlayer material in composites by forming strong bonding between different matrices, which sheds light on the design of impact protection composite materials. To further investigate the impact resistance and strengthening mechanism of Ti8C5, a pilot Molecular Dynamics (MD) study utilizing comb3 potential is carried out on a Ti8C5 nanosheet by subjecting it to hypervelocity impacts. The deformation behaviour of Ti8C5 and the related impact resist mechanisms are assessed in this research. At a low impact velocity ~0.5 km/s, the main resonance frequency of Ti8C5 is 11.9 GHz and its low Q factor (111.9) indicates a decent energy damping capability, which would eliminate the received energy in an interfacial reflection process and weaken the shock waves for Ti8C5 strengthened composites. As the impact velocity increases above the threshold of 1.8 km/s, Ti8C5 demonstrates brittle behaviour, which is signified by its insignificant out-of-plane deformation prior to crack initiation. When tracking atomic Von Mises stress distribution, the elastic wave propagation velocity of Ti8C5 is calculated to be 5.34 and 5.90 km/s for X and Y directions, respectively. These figures are inferior compared with graphene and copper, which indicate slower energy delocalization rates and thus less energy dissipation via deformation is expected prior to bond break. However, because of its relatively small mass density comparing with copper, Ti8C5 presents superior specific penetration. This study provides a fundamental understanding of the deformation and penetration mechanisms of titanium carbide nanosheets under impact, which is crucial in order to facilitate emerging impact protection applications for titanium carbide-related composites

    Analysis of the ASMT Gene Family in Pepper (Capsicum annuum L.): Identification, Phylogeny, and Expression Profiles

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    Acetylserotonin methyltransferase (ASMT) in plant species, one of the most important enzymes in melatonin biosynthesis, plays a rate-limiting role in the melatonin production. In this study, based on the whole genome sequence, we performed a systematic analysis for the ASMT gene family in pepper (Capsicum annuum L.) and analyzed their expression profiles during growth and development, as well as abiotic stresses. The results showed that at least 16 CaASMT genes were identified in the pepper genome. Phylogenetic analyses of all the CaASMTs were divided into three groups (group I, group II, and group III) with a high bootstrap value. Through the online MEME tool, six distinct motifs (motif 1 to motif 6) were identified. Chromosome location found that most CaASMT genes were mapped in the distal ends of the pepper chromosomes. In addition, RNA-seq analysis revealed that, during the vegetative and reproductive development, the difference in abundance and distinct expression patterns of these CaASMT genes suggests different functions. The qRT-PCR analysis showed that high abundance of CaASMT03, CaASMT04, and CaASMT06 occurred in mature green fruit and mature red fruit. Finally, using RNA-seq and qRT-PCR technology, we also found that several CaASMT genes were induced under abiotic stress conditions. The results will not only contribute to elucidate the evolutionary relationship of ASMT genes but also ascertain the biological function in pepper plant response to abiotic stresses

    Genome-wide characterization of ascorbate peroxidase gene family in pepper (Capsicum annuum L.) in response to multiple abiotic stresses

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    Pepper is widely grown all over the world, so it faces many abiotic stresses, such as drought, high temperature, low temperature, salt damage, and so on. Stresses causing the accumulation of reactive oxidative species (ROS) in plants are removed by antioxidant defense systems, and ascorbate peroxidase (APX) is an important antioxidant enzyme. Therefore, the present study performed genome-wide identification of the APX gene family in pepper. We identified nine members of the APX gene family in the pepper genome according to the APX proteins’ conserved domain in Arabidopsis thaliana. The physicochemical property analysis showed that CaAPX3 had the longest protein sequence and the largest molecular weight of all genes, while CaAPX9 had the shortest protein sequence and the smallest MW. The gene structure analysis showed that CaAPXs were composed of seven to 10 introns. The CaAPX genes were divided into four groups. The APX genes of groups I and IV were localized in the peroxisomes and chloroplasts, respectively; the group II genes were localized in the chloroplasts and mitochondria; and the group III genes were located in the cytoplasm and extracell. The conservative motif analysis showed that all APX genes in the pepper had motif 2, motif 3, and motif 5. The APX gene family members were distributed on five chromosomes (Chr. 2, 4, 6, 8, and 9). The cis-acting element analysis showed that most CaAPX genes contain a variety of cis-elements related to plant hormones and abiotic stress. RNA-seq expression analysis showed that the expression patterns of nine APXs were different in vegetative and reproductive organs at different growth and development stages. In addition, the qRT-PCR analysis of the CaAPX genes revealed significant differential expression in response to high temperature, low temperature, and salinity stresses in leaf tissue. In conclusion, our study identified the APX gene family members in the pepper and predicted the functions of this gene family, which would provide resources for further functional characterization of CaAPX genes

    HSF1 Stimulates Glutamine Transport by Super-Enhancer-Driven lncRNA LINC00857 in Colorectal Cancer

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    Super enhancers are critical for the gene transcription responsible for cell fate by interacting with transcription factors. However, the relevance of HSF1 to super enhancers in tumors remains obscure. We profiled H3K27ac enrichment by chromatin immunoprecipitation sequencing. HSF1-mediated lncRNAs were identified by lncRNA microarray. The characteristics of LINC00857 were explored by in vitro and in vivo assays. The mechanism was studied via chromatin immunoprecipitation, RNA immunoprecipitation, and HSF1/ANXA11 knockout mice. We found that super enhancers occupied multiple gene loci in colorectal cancer. We screened out an HSF1-mediated super enhancer, lncRNA-LINC00857, which exerts its characteristics in promoting cell growth via regulating glutamine metabolism. Notably, HSF1 could stimulate the super-enhancer activity of LINC00857 by the enrichment of acetyltransferase P300 to its gene loci, contributing to LINC00857 transcription. In turn, nuclear LINC00857 cooperated with HSF1 to promote ANXA11 transcription, which modulated SLC1A5/ASCT2 protein expression by binding competitively to miR-122-5p. The knockout of ANXA11 attenuated colorectal cancer formation in vivo. Collectively, we shed light on a closely cooperative machinery between HSF1 and super enhancers. HSF1 could stimulate acetyltransferase P300-mediated super-enhancer activity to facilitate LINC00857 expression, contributing to SLC1A5-mediated glutamine transport. Targeting the HSF1/LINC00857/ANXA11 axis may provide a valuable therapeutic strategy against colorectal cancer

    Pan-Cancer Analysis of the Roles and Driving Forces of RAB42

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    RAB42 is a member of the RAS family. However, the roles and driving forces for RAB42 in tumors remain elusive. In this study, we performed a comprehensive pan-cancer analysis of the roles and regulatory mechanisms of RAB42 using bioinformatics and experiments. Online databases such as Sanger Box, ACLBI and TIDE were used to search for the expression levels, prognostic value and immune features of RAB42. We observed that RAB42 expression was upregulated in most tumors and was closely associated with poor prognosis. Enrichment analysis indicated that RAB42 was related to multiple biological functions, especially the immune process. RAB42 expression had a positive correlation with immune cell infiltration and immune checkpoint gene expression. RAB42 had a high predictive value for immunotherapy efficiency. Our study screened out susceptible drugs for the RAB42 protein by sensitivity analysis and virtual screening. Many key driver genes such as TP53 contributed to RAB42 expression. DNA methylation, super-enhancer and non-coding RNAs were the epigenetic factors responsible for RAB42 expression. In brief, RAB42 could serve as a diagnostic and prognostic biomarker in many tumor types. RAB42 might be a predictive biomarker and a new target for immunotherapy. Genetic and epigenetic factors were essential for RAB42 overexpression in tumors

    Computational fluid dynamics simulations at micro-scale stenosis for microfluidic thrombosis model characterization

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    Platelet aggregation plays a central role in pathological thrombosis, preventing healthy physiological blood flow within the circulatory system. For decades, it was believed that platelet aggregation was primarily driven by soluble agonists such as thrombin, adenosine diphosphate and thromboxane A2. However, recent experimental findings have unveiled an intriguing but complementary biomechanical mechanism-the shear rate gradients generated from flow disturbance occurring at sites of blood vessel narrowing, otherwise known as stenosis, may rapidly trigger platelet recruitment and subsequent aggregation. In our Nature Materials 2019 paper [1], we employed microfluidic devices which incorporated micro-scale stenoses to elucidate the molecular insights underlying the prothrombotic effect of blood flow disturbance. Nevertheless, the rheological mechanisms associated with this stenotic microfluidic device are poorly characterized. To this end, we developed a computational fluid dynamics (CFD) simulation approach to systematically analyze the hemodynamic influence of bulk flow mechanics and flow medium. Grid sensitivity studies were performed to ensure accurate and reliable results. Interestingly, the peak shear rate was significantly reduced with the device thickness, suggesting that fabrication of microfluidic devices should retain thicknesses greater than 50 µm to avoid unexpected hemodynamic aberration, despite thicker devices raising the cost of materials and processing time of photolithography. Overall, as many groups in the field have designed microfluidic devices to recapitulate the effect of shear rate gradients and investigate platelet aggregation, our numerical simulation study serves as a guideline for rigorous design and fabrication of microfluidic thrombosis models.</p

    Image1_Exploring the oncogenic roles of LINC00857 in pan-cancer.pdf

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    Although aberrant LINC00857 expression may play a key role in oncogenesis, no research has analyzed the pan-cancer oncogenic roles of LINC00857, particularly in tumor immunology. Here, we integrated data from several databases to analyze the characteristics of LINC00857 in pan-cancer. We found that LINC00857 was overexpressed and correlated with a poor prognosis in a variety of cancers. Furthermore, high-expression of LINC00857 was negatively associated with immune cell infiltration and immune checkpoint gene expression. Notably, LINC00857 expression was negatively related to microsatellite instability and tumor mutation burden in colorectal cancer, implying poor reaction to immunotherapy when LINC00857 was highly expressed. Targeting LINC00857 could dramatically impair the proliferative ability of colorectal cancer cells. After RNA-sequencing in HCT116 cells, gene set enrichment analysis showed that LINC00857 may accelerate cancer progression by inhibiting the ferroptosis pathway and promoting glycolipid metabolism in colorectal cancer. Screening by weighted gene co-expression network analysis determined PIWIL4 as a target of LINC00857, which also performed an immunosuppressive role in colorectal cancer. Based on the structure of PIWIL4, a number of small molecule drugs were screened out by virtual screening and sensitivity analysis. In summary, LINC00857 expression was closely correlated with an immunosuppressive microenvironment and may be a novel diagnostic and prognostic biomarker for diverse cancers. The LINC00857/PIWIL4 axis may be predictive biomarkers for immunotherapy and valuable molecular targets for malignant tumors.</p

    Pregnancy, pregnancy loss and the risk of cardiovascular disease in Chinese women: findings from the China Kadoorie Biobank

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    Background Pregnancy and pregnancy loss may be linked to cardiovascular disease (CVD). However, the evidence is still inconsistent, especially in East Asians where reproductive patterns differ importantly from those in the West. We examined the associations of pregnancy, miscarriage, induced abortion, and stillbirth with CVD incidence among Chinese women. Methods In 2004-08, the nationwide China Kadoorie Biobank recruited 302 669 women aged 30-79 years from 10 diverse localities. During 7 years of follow-up, 43 968 incident cases of circulatory disease, 14 440 of coronary heart disease (CHD), and 19 925 of stroke (including 11 430 ischemic and 2 170 haemorrhagic strokes), were recorded among 289,573 women without prior CVD at baseline. Cox regression yielded multiple-adjusted hazard ratios (HRs) for CVD risks associated with pregnancy outcomes. Results Overall, 99% of women had been pregnant and among them 10%, 53%, and 7% reported having a history of miscarriage, induced abortion, and stillbirth, respectively. Each additional pregnancy was associated with an adjusted HR of 1.03 (95% CI: 1.02; 1.04) for circulatory disease. A history of miscarriage, induced abortion, and stillbirth, respectively, were associated with adjusted HRs of 1.04 (1.01; 1.07), 1.04 (1.02; 1.07), and 1.07 (1.03; 1.11) for circulatory disease. The relationship was stronger with recurrent pregnancy loss; adjusted HRs for each additional loss being 1.04 (1.00; 1.09) for miscarriage, 1.02 (1.01; 1.04) for induced abortion, and 1.04 (1.00; 1.08) for stillbirth. Conclusion Among Chinese women, increases in pregnancy, and a history and recurrence of miscarriage, induced abortion, and stillbirth are each associated with a higher risk of CVD.</p
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