118 research outputs found

    Efficient and Fast Synthesis of Few-Layer Black Phosphorus via Microwave-Assisted Liquid-Phase Exfoliation

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    High‐quality, few‐layer black‐phosphorus (BP) flakes are prepared in a common organic solvent with very short processing times using microwave‐assisted liquid‐phase exfoliation. A comprehensive range of analysis, combined with density‐functional theory calculations, confirms that the product prepared using the microwave technique is few‐layer BP with small‐ and large‐area flakes. The suspended exfoliated BP sheets show excellent stability, while samples dispersed onto silicon from the suspensions exhibit low oxidation levels after several days in ambient conditions. This straightforward synthesis method is facile, efficient, and extremely fast, and does not involve use of any surfactant or ultrasonication steps and will facilitate future development of phosphorene research

    Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures

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    Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) represent rare and common forms of GnRH deficiency, respectively. Both CDGP and CHH present with delayed puberty, and the distinction between these two entities during early adolescence is challenging. More than 30 genes have been implicated in CHH, while the genetic basis of CDGP is poorly understood. We characterized and compared the genetic architectures of CHH and CDGP, to test the hypothesis of a shared genetic basis between these disorders. Exome sequencing data were used to identify rare variants in known genes in CHH ( <i>n</i>  = 116), CDGP ( <i>n</i>  = 72) and control cohorts ( <i>n</i>  = 36 874 ExAC and <i>n</i>  = 405 CoLaus). Mutations in at least one CHH gene were found in 51% of CHH probands, which is significantly higher than in CDGP (7%, <i>P</i>  = 7.6 × 10 <sup>-11</sup> ) or controls (18%, <i>P</i>  = 5.5 × 10 <sup>-12</sup> ). Similarly, oligogenicity (defined as mutations in more than one gene) was common in CHH patients (15%) relative to CDGP (1.4%, <i>P</i>  = 0.002) and controls (2%, <i>P</i>  = 6.4 × 10 <sup>-7</sup> ). Our data suggest that CDGP and CHH have distinct genetic profiles, and this finding may facilitate the differential diagnosis in patients presenting with delayed puberty

    CYLD Enhances Severe Listeriosis by Impairing IL-6/STAT3-Dependent Fibrin Production

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    The facultative intracellular bacterium Listeria monocytogenes (Lm) may cause severe infection in humans and livestock. Control of acute listeriosis is primarily dependent on innate immune responses, which are strongly regulated by NF-kappa B, and tissue protective factors including fibrin. However, molecular pathways connecting NF-kappa B and fibrin production are poorly described. Here, we investigated whether the deubiquitinating enzyme CYLD, which is an inhibitor of NF-kappa B-dependent immune responses, regulated these protective host responses in murine listeriosis. Upon high dose systemic infection, all C57BL/6 Cyld(-/-) mice survived, whereas 100% of wildtype mice succumbed due to severe liver pathology with impaired pathogen control and hemorrhage within 6 days. Upon in vitro infection with Lm, CYLD reduced NF-kappa B-dependent production of reactive oxygen species, interleukin (IL)-6 secretion, and control of bacteria in macrophages. Furthermore, Western blot analyses showed that CYLD impaired STAT3-dependent fibrin production in cultivated hepatocytes. Immunoprecipitation experiments revealed that CYLD interacted with STAT3 in the cytoplasm and strongly reduced K63-ubiquitination of STAT3 in IL-6 stimulated hepatocytes. In addition, CYLD diminished IL-6-induced STAT3 activity by reducing nuclear accumulation of phosphorylated STAT3. In vivo, CYLD also reduced hepatic STAT3 K63-ubiquitination and activation, NF-kappa B activation, IL-6 and NOX2 mRNA production as well as fibrin production in murine listeriosis. In vivo neutralization of IL-6 by anti-IL-6 antibody, STAT3 by siRNA, and fibrin by warfarin treatment, respectively, demonstrated that IL-6-induced, STAT3-mediated fibrin production significantly contributed to protection in Cyld(-/-) mice. In addition, in vivo Cyld siRNA treatment increased STAT3 phosphorylation, fibrin production, pathogen control and survival of Lm-infected WT mice illustrating that therapeutic inhibition of CYLD augments the protective NF-kappa B/IL-6/STAT3 pathway and fibrin production

    Laying waste to mercury: inexpensive sorbents made from sulfur and recycled cooking oils

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    Mercury pollution threatens the environment and human health across the globe. This neurotoxic substance is encountered in artisanal gold mining, coal combustion, oil and gas refining, waste incineration, chloralkali plant operation, metallurgy, and areas of agriculture in which mercury-rich fungicides are used. Thousands of tonnes of mercury are emitted annually through these activities. With the Minamata Convention on Mercury entering force this year, increasing regulation of mercury pollution is imminent. It is therefore critical to provide inexpensive and scalable mercury sorbents. The research herein addresses this need by introducing low-cost mercury sorbents made solely from sulfur and unsaturated cooking oils. A porous version of the polymer was prepared by simply synthesising the polymer in the presence of a sodium chloride porogen. The resulting material is a rubber that captures liquid mercury metal, mercury vapour, inorganic mercury bound to organic matter, and highly toxic alkylmercury compounds. Mercury removal from air, water and soil was demonstrated. Because sulfur is a by-product of petroleum refining and spent cooking oils from the food industry are suitable starting materials, these mercury-capturing polymers can be synthesised entirely from waste and supplied on multi-kilogram scales. This study is therefore an advance in waste valorisation and environmental chemistry.Max J. H. Worthington, Renata L. Kucera, Inês S. Albuquerque, Christopher T. Gibson, Alexander Sibley, Ashley D. Slattery, Jonathan A. Campbell, Salah F. K. Alboaiji, Katherine A. Muller, Jason Young, Nick Adamson, Jason R. Gascooke, Deshetti Jampaiah, Ylias M. Sabri, Suresh K. Bhargava, Samuel J. Ippolito, David A. Lewis, Jamie S. Quinton, Amanda V. Ellis, Alexander Johs, Gonçalo J.L. Bernardes and Justin M. Chalke

    Functionalized Positive Nanoparticles Reduce Mucin Swelling and Dispersion

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    Multi-functionalized nanoparticles (NPs) have been extensively investigated for their potential in household and commercial products, and biomedical applications. Previous reports have confirmed the cellular nanotoxicity and adverse inflammatory effects on pulmonary systems induced by NPs. However, possible health hazards resulting from mucus rheological disturbances induced by NPs are underexplored. Accumulation of viscous, poorly dispersed, and less transportable mucus leading to improper mucus rheology and dysfunctional mucociliary clearance are typically found to associate with many respiratory diseases such as asthma, cystic fibrosis (CF), and COPD (Chronic Obstructive Pulmonary Disease). Whether functionalized NPs can alter mucus rheology and its operational mechanisms have not been resolved. Herein, we report that positively charged functionalized NPs can hinder mucin gel hydration and effectively induce mucin aggregation. The positively charged NPs can significantly reduce the rate of mucin matrix swelling by a maximum of 7.5 folds. These NPs significantly increase the size of aggregated mucin by approximately 30 times within 24 hrs. EGTA chelation of indigenous mucin crosslinkers (Ca2+ ions) was unable to effectively disperse NP-induced aggregated mucins. Our results have demonstrated that positively charged functionalized NPs can impede mucin gel swelling by crosslinking the matrix. This report also highlights the unexpected health risk of NP-induced change in mucus rheological properties resulting in possible mucociliary transport impairment on epithelial mucosa and related health problems. In addition, our data can serve as a prospective guideline for designing nanocarriers for airway drug delivery applications

    Functionalized carboxyl nanoparticles enhance mucus dispersion and hydration

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    Luminal accumulation of viscous, poorly hydrated, and less transportable mucus has been associated with altered mucus rheology and reduced mucociliary clearance. These symptoms are some of the cardinal clinical manifestations found throughout major respiratory diseases as well as gastrointestinal and digestive disorders. Applications of current mucolytics may yield short-term improvements but are continuously challenged by undesirable side-effects. While nanoparticles (NPs) can interact with mucin polymers, whether functionalized NPs can rectify mucus rheology is unknown. Herein, we report that carboxyl-functionalized NPs (24 nm and 120 nm) dramatically reduced mucin gel size and accelerated mucin matrix hydration rate (diffusivity). Our results suggest that carboxyl-functionalized NPs disperse mucin gels possibly by enhancing network hydration. This report highlights the prospective usages of carboxyl-functionalized NPs as a novel mucus dispersant or mucolytic agent in adjusting mucus rheological properties and improving mucociliary transport to relieve clinical symptoms of patients suffering from relevant diseases

    Meeting the adoption support needs of adopted adults who have been abused in their adoptive family: Lessons from historical placements

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    This article focuses on a group whose voice is rarely heard: adopted adults who have been abused or neglected within their adoptive family. The findings are drawn from a larger study of post-adoption services and suggest that the abuse and neglect of children by adoptive family members may be more common historically than has been hitherto acknowledged. The article considers this finding in the context of the changes that have occurred in adoption legislation, policy and practice since these adults were placed. It highlights barriers to effective support for abused adopted adults and discusses their support needs. By looking at one aspect of what can go wrong in adoptions – abuse and neglect perpetrated by adoptive family members – it is argued that appropriate support will not be forthcoming unless we are truly hearing what people want. Suggestions are made regarding the development of support services for abused adopted adults and their birth parents and opportunities for adopted children to disclose maltreatment
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