1,443 research outputs found

    Anaesthesia for emergency caesarean section in a patient with large anterior mediastinal tumour presenting as intrathoracic airway compression and superior vena cava obstruction

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    Anterior mediastinal mass is an uncommon pathology that presents significant anaesthetic challenges because of cardiopulmonary compromise. We present a case that presented in the third trimester of pregnancy with severe breathlessness, orthopnoea, and symptoms of superior vena cava obstruction. The patient had emergency Caesarean section under epidural anaesthesia with a good outcome. The paper discusses the relevant perioperative considerations for this complex scenario and reviews reports of similar conditions.published_or_final_versio

    Design of dry powder formulations of pH responsive peptide/plasmid DNA complexes for pulmonary delivery

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    Poster Presentation: no. 13PS50Respiratory diseases are substantial public health problems around the world. Recently, nucleic acid was developed as a potential therapeutic strategy to tackle a series of lung diseases. Delivery still poses one of the major challenges for their clinical application. pH responsive peptides containing either histidine or derivatives of 2,3-diaminopropionic acid (Dap) can mediate effective DNA transfection in lung epithelial cells with the latter remaining effective even in the presence of lung surfactant containing bronchoalveolar fluid (BALF), which make them promising vectors for delivering therapeutic nucleic acid to the airways .....published_or_final_versio

    Polysaccharopeptide enhanced the anti-cancer effect of gamma-tocotrienol through activation of AMPK

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    BACKGROUND: Prostate cancer (PCa) frequently relapses after hormone ablation therapy. Unfortunately, once progressed to the castration resistant stage, the disease is regarded as incurable as prostate cancer cells are highly resistant to conventional chemotherapy. METHOD: We recently reported that the two natural compounds polysaccharopeptide (PSP) and Gamma-tocotrienols (gamma-T3) possessed potent anti-cancer activities through targeting of CSCs. In the present study, using both prostate cancer cell line and xenograft models, we seek to investigate the therapeutic potential of combining gamma-T3 and PSP in the treatment of prostate cancer. RESULT: We showed that in the presence of PSP, gamma-T3 treatment induce a drastic activation of AMP-activated protein kinase (AMPK). This was accompanied with inactivation of acetyl-CoA carboxylase (ACC), as evidenced by the increased phosphorylation levels at Ser 79. In addition, PSP treatment also sensitized cancer cells toward gamma-T3-induced cytotoxicity. Furthermore, we demonstrated for the first time that combination of PSP and gamma-T3 treaments significantly reduced the growth of prostate tumor in vivo. CONCLUSION: Our results indicate that PSP and gamma-T3 treaments may have synergistic anti-cancer effect in vitro and in vivo, which warrants further investigation as a potential combination therapy for the treatment of cancer.published_or_final_versio

    Laser powder bed fusion of high-strength and corrosion-resistant Inconel alloy 725

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    The development of additive manufacturing, or three-dimensional (3D) printing, technologies has produced breakthroughs in the design and manufacturing of products by enhancing design freedom and minimising manufacturing steps. In addition, the complex, unique microstructures imparted by the additive processes offer prospects of unprecedented advances to produce high-performance metal alloys for high-temperature and corrosive environments. Here, we present the first additive manufacturing of Inconel alloy 725, an advanced nickel-base superalloy that is the widely accepted gold standard material of choice for oil and gas, chemical, and marine applications. We explore the printability of Inconel alloy 725 and identify a wide processing space to build material with a crack- and near-pore-free microstructure. The conventionally heat-treated Inconel alloy 725 has an equiaxed, near-fully recrystallised microstructure containing copious twin boundaries and nano-precipitates. It also displays promising tensile properties and corrosion resistance compared to its wrought counterpart. Our work opens the door toward additive manufacturing of Inconel alloy 725 components with optimised microstructure and topology geometry for applications in harsh environments

    Expression Analysis and Interaction Protein Screening of CRY1 in Strawberry

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    Cryptochrome 1 (CRY1), a main blue light receptor protein, plays a significant role in several biological processes. However, the expression patterns and function of CRY1 in strawberry have not been identified. Here, the expression profile of CRY1 in different tissues and developmental stages of strawberry fruit, and expression patterns response to abiotic stresses (low temperature, salt and drought) were analyzed. Its subcellular localization, interaction proteins and heterologous overexpression in tobacco were also investigated. The results showed that CRY1 was mainly expressed in leaves and fruits with an expression peak at the initial red stage in strawberry fruit. Abiotic stresses could significantly induce the expression of CRY1. The CRY1 protein was located in both nucleus and cytoplasm. Five proteins (CSN5a-like, JAZ5, eIF3G. NF-YC9, and NDUFB9) interacting with CRY1 were discovered. Genes related flowering times, such as HY5 and CO, in three overexpressed FaCRY1 tobacco lines, were significantly upregulated. Taken together, our results suggested CRY1 have a broad role in biological processes in strawberry

    TSC1/2 mutations define a molecular subset of HCC with aggressive behaviour and treatment implication

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    Objective We investigated the mutational landscape of mammalian target of rapamycin (mTOR) signalling cascade in hepatocellular carcinomas (HCCs) with chronic HBV background, aiming to evaluate and delineate mutation-dependent mechanism of mTOR hyperactivation in hepatocarcinogenesis. Design We performed next-generation sequencing on human HCC samples and cell line panel. Systematic mutational screening of mTOR pathway-related genes was undertaken and mutant genes were evaluated based on their recurrence. Protein expressions of tuberous sclerosis complex (TSC)1, TSC2 and pRPS6 were assessed by immunohistochemistry in human HCC samples. Rapamycin sensitivity was estimated by colony-formation assay in HCC cell lines and the treatment was further tested using our patient-derived tumour xenograft (PDTX) models. Results We identified and confirmed multiple mTOR components as recurrently mutated in HBV-associated HCCs. Of significance, we detected frequent (16.2%, n=18/111) mutations of TSC1 and TSC2 genes in the HCC samples. The spectrum of TSC1/2 mutations likely disrupts the endogenous gene functions in suppressing the downstream mTOR activity through different mechanisms and leads to more aggressive tumour behaviour. Mutational disruption of TSC1 and TSC2 was also observed in HCC cell lines and our PDTX models. TSC-mutant cells exhibited reduced colony-forming ability on rapamycin treatment. With the use of biologically relevant TSC2-mutant PDTXs, we demonstrated the therapeutic benefits of the hypersensitivity towards rapamycin treatment. Conclusions Taken together, our findings suggest the significance of previously undocumented mutation-dependent mTOR hyperactivation and frequent TSC1/2 mutations in HBV-associated HCCs. They define a molecular subset of HCC having genetic aberrations in mTOR signalling, with potential significance of effective specific drug therapy.published_or_final_versio

    Evolutionary analysis of mitochondrially encoded proteins of toad-headed lizards, Phrynocephalus, along an altitudinal gradient.

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    BACKGROUND: Animals living at high altitude must adapt to environments with hypoxia and low temperatures, but relatively little is known about underlying genetic changes. Toad-headed lizards of the genus Phrynocephalus cover a broad altitudinal gradient of over 4000 m and are useful models for studies of such adaptive responses. In one of the first studies to have considered selection on mitochondrial protein-coding regions in an ectothermic group distributed over such a wide range of environments, we analysed nineteen complete mitochondrial genomes from all Chinese Phrynocephalus (including eight genomes sequenced for the first time). Initial analyses used site and branch-site model (program: PAML) approaches to examine nonsynonymous: synonymous substitution rates across the mtDNA tree. RESULTS: Ten positively selected sites were discovered, nine of which corresponded to subunits ND2, ND3, ND4, ND5, and ND6 within the respiratory chain enzyme mitochondrial Complex I (NADH Coenzyme Q oxidoreductase). Four of these sites showed evidence of general long-term selection across the group while the remainder showed evidence of episodic selection across different branches of the tree. Some of these branches corresponded to increases in altitude and/or latitude. Analyses of physicochemical changes in protein structures revealed that residue changes at sites that were under selection corresponded to major functional differences. Analyses of coevolution point to coevolution of selected sites within the ND4 subunit, with key sites associated with proton translocation across the mitochondrial membrane. CONCLUSIONS: Our results identify mitochondrial Complex I as a target for environment-mediated selection in this group of lizards, a complex that frequently appears to be under selection in other organisms. This makes these lizards good candidates for more detailed future studies of molecular evolution

    Synthesis and Application of Carbon–Iron Oxide Microspheres’ Black Pigments in Electrophoretic Displays

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    Carbon–iron oxide microspheres’ black pigments (CIOMBs) had been prepared via ultrasonic spray pyrolysis of aqueous solutions containing ferrous chloride and glucose. Due to the presence of carbon, CIOMBs not only exhibited remarkably acid resistance, but also could be well dispersed in both polar solvents and nonpolar solvent. Finally, dispersions of hollow CIOMBs in tetrachloroethylene had successfully been applied in electrophoretic displays

    Structural and bonding transformation of Al0.67CrCoCuFeNi high-entropy alloys during quenching

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    Structural and bonding transformation of the Al0.67CrCoFeNi high-entropy alloys (HEA) during&nbsp;quenching&nbsp;is investigated by molecular dynamics simulations. At a high cooling rate, some short-ranged ordered clusters, such as FCC, HCP and BCC&nbsp;crystalline&nbsp;clusters are already present in the almost amorphous HEAs. When the cooling rate decreases, the atoms become packed more orderly and ultimately form a nano-polycrystalline structure dominated by FCC structures. The BCC structures appear only as an intermediate state acting on the course of&nbsp;crystallization, while the HCP structure can be viewed as the precursor of the malposed FCC structure due to the identical first neighbor distances. In liquid HEAs, the low-symmetry and low-coordination bond pairs, either transform to high-symmetry and high-coordination 1551 bond pairs, or transform to 1(5,4)41 bond pairs for FCC structure and 1661 bond pairs for an HCP structure, depending on the cooling rates. This study will contribute to a better understanding of the essential phase change in HEAs.</p
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