Structural investigations into colour-tuneable fluorescent InZnP-based quantum dots from zinc carboxylate and aminophosphine precursors.

Fluorescent InP-based quantum dots have emerged as valuable nanomaterials for display technologies, biological imaging, and optoelectronic applications. The inclusion of zinc can enhance both their emissive and structural properties and reduce interfacial defects with ZnS or CdS shells. However, the sub-particle distribution of zinc and the role this element plays often remains unclear, and it has previously proved challenging to synthesise Zn-alloyed InP-based nanoparticles using aminophosphine precursors. In this report, we describe the synthesis of alloyed InZnP using zinc carboxylates, achieving colour-tuneable fluorescence from the unshelled core materials, followed by a one-pot ZnS or CdS deposition using diethyldithiocarbamate precursors. Structural analysis revealed that the "core/shell" particles synthesised here were more accurately described as homogeneous extended alloys with the constituent shell elements diffusing through the entire core, including full-depth inclusion of zinc.

Voriconazole-Associated Periostitis: New Insights into Pathophysiology and Management.

Voriconazole-associated periostitis (VAP) is an underrecognized and unpredictable side effect of long-term voriconazole therapy. We report two cases of VAP occurring in the post-transplant setting: a 68-year-old lung transplant recipient who required ongoing voriconazole therapy, in whom urinary alkalinization was used to promote fluoride excretion and minimize voriconazole-related skeletal toxicity, and a 68-year-old stem-cell transplant recipient with a high voriconazole dose requirement, identified on pharmacogenomic testing to be a CYP2C19 ultrarapid metabolizer, the dominant enzyme in voriconazole metabolism. This is the first reported case of pharmacogenomic profiling in VAP and may explain the variability in individual susceptibility to this uncommon adverse effect. Our findings provide new insights into both the management and underlying pathophysiology of VAP. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Author Correction: Area-based conservation in the twenty-first century.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Area-based conservation in the twenty-first century.

Humanity will soon define a new era for nature-one that seeks to transform decades of underwhelming responses to the global biodiversity crisis. Area-based conservation efforts, which include both protected areas and other effective area-based conservation measures, are likely to extend and diversify. However, persistent shortfalls in ecological representation and management effectiveness diminish the potential role of area-based conservation in stemming biodiversity loss. Here we show how the expansion of protected areas by national governments since 2010 has had limited success in increasing the coverage across different elements of biodiversity (ecoregions, 12,056 threatened species, 'Key Biodiversity Areas' and wilderness areas) and ecosystem services (productive fisheries, and carbon services on land and sea). To be more successful after 2020, area-based conservation must contribute more effectively to meeting global biodiversity goals-ranging from preventing extinctions to retaining the most-intact ecosystems-and must better collaborate with the many Indigenous peoples, community groups and private initiatives that are central to the successful conservation of biodiversity. The long-term success of area-based conservation requires parties to the Convention on Biological Diversity to secure adequate financing, plan for climate change and make biodiversity conservation a far stronger part of land, water and sea management policies.

Sixty years of tracking conservation progress using the World Database on Protected Areas.

The world's protected area network is constantly changing, and the dynamics of this network are tracked using the World Database on Protected Areas (WDPA). This database evolved from a list of protected areas first mandated by the United Nations in 1959, and it now informs the key indicators that track progress toward area-based conservation targets. In this capacity, the WDPA illuminates the role of protected areas in advancing a range of international objectives and agreements, including the Convention on Biological Diversity and the Sustainable Development Goals. Despite ongoing challenges in maintaining such a complex global dataset, the WDPA is continuously improving and taking advantage of new technology, making it widely applicable to diverse users, including those in sectors far from its original intended audience. In the future, the WDPA will expand to include areas that contribute to conservation and sustainable use outside of formal protected areas, and will increasingly link to other key global datasets. These innovations in the way the WDPA is managed and used will deliver vital knowledge to support a sustainable future for biodiversity and people globally.

Dynamics in the global protected-area estate since 2004.

Nations of the world have committed to a number of goals and targets to address global environmental challenges. Protected areas have for centuries been a key strategy in conservation and play a major role in addressing current challenges. The most important tool used to track progress on protected-area commitments is the World Database on Protected Areas (WDPA). Periodic assessments of the world's protected-area estate show steady growth over the last 2 decades. However, the current method, which uses the latest version of the WDPA, does not show the true dynamic nature of protected areas over time and does not provide information on sites removed from the WDPA. In reality, this method can only show growth or remain stable. We used GIS tools in an approach to assess protected-area change over time based on 12 temporally distinct versions of the WDPA that quantify area added and removed from the WDPA annually from 2004 to 2016. Both the narrative of continual growth of protected area and the counter-narrative of protected area removal were overly simplistic. The former because growth was almost entirely in the marine realm and the latter because some areas removed were reprotected in later years. On average 2.5 million km2 was added to the WDPA annually and 1.1 million km2 was removed. Reasons for the inclusion and removal of protected areas in the WDPA database were in part due to data-quality issues but also to on-the-ground changes. To meet the 17% protected-area component of Aichi Biodiversity Target 11 by 2020, which stood at 14.7% in 2016, either the rate of protected-area removal must decrease or the rate of protected-area designation and addition to the WDPA must increase.

Dinámica de los Bienes de las Áreas Protegidas desde 2004 Resumen Países alrededor del mundo se han comprometido con un número de metas y objetivos para tratar los retos ambientales mundiales. Las áreas protegidas han funcionado durante siglos como una estrategia clave en la conservación y juegan un papel importante en cómo se manejan los retos actuales. La herramienta más importante que se usa para rastrear el progreso de los compromisos con las áreas protegidas es la Base de Datos Mundial de las Áreas Protegidas (WDPA, en inglés). Las evaluaciones periódicas de los bienes de las áreas protegidas muestran un crecimiento constante durante las últimas dos décadas. Sin embargo, el método actual, que usa la versión más reciente de la WDPA, no muestra la verdadera naturaleza dinámica de las áreas protegidas a lo largo del tiempo y no proporciona información sobre sitios que han sido removidos de la WDPA. En realidad este método sólo puede mostrar crecimiento o permanecer estable. Usamos herramientas de SIG en una estrategia para evaluar el cambio de las áreas protegidas a lo largo del tiempo con base en doce versiones temporalmente distintas de la WDPA que cuantifican las áreas añadidas o removidas de la WDPA anualmente desde 2004 hasta 2016. Tanto la narrativa del crecimiento continuo de un área protegida como la contra-narrativa de la eliminación de un área protegida fueron exageradamente simplistas. La primera se debe a que el crecimiento ocurrió casi en su mayoría en el dominio marino y la segunda a que algunas áreas eliminadas fueron reprotegidas años después. En promedio se añadieron 2.5 millones de km2 a la WDPA anualmente y 1.1 millones de km2 fueron removidos. Las razones para la inclusión y la eliminación de las áreas protegidas de la base de datos de la WDPA se debieron en parte a temas de calidad de datos pero también a cambios hechos sobre la marcha. Para lograr el 17% del componente de áreas protegidas del Objetivo 11 de Biodiversidad de Aichi para el 2020, el cual se encontraba al 14.7% en 2016, se debe disminuir la tasa de eliminación de áreas protegidas o se debe incrementar la tasa de designación y suma de áreas protegidas a la WDPA.

Scalable Patterning of Encapsulated Black Phosphorus.

Atomically thin black phosphorus (BP) has attracted considerable interest due to its unique properties, such as an infrared band gap that depends on the number of layers and excellent electronic transport characteristics. This material is known to be sensitive to light and oxygen and degrades in air unless protected with an encapsulation barrier, limiting its exploitation in electrical devices. We present a new scalable technique for nanopatterning few layered BP by direct electron beam exposure of encapsulated crystals, achieving a spatial resolution down to 6 nm. By encapsulating the BP with single layer graphene or hexagonal boron nitride (hBN), we show that a focused electron probe can be used to produce controllable local oxidation of BP through nanometre size defects created in the encapsulation layer by the electron impact. We have tested the approach in the scanning transmission electron microscope (STEM) and using industry standard electron beam lithography (EBL). Etched regions of the BP are stabilized by a thin passivation layer and demonstrate typical insulating behavior as measured at 300 and 4.3 K. This new scalable approach to nanopatterning of thin air sensitive crystals has the potential to facilitate their wider use for a variety of sensing and electronics applications.

A Fragment-Derived Clinical Candidate for Antagonism of X-Linked and Cellular Inhibitor of Apoptosis Proteins: 1-(6-[(4-Fluorophenyl)methyl]-5-(hydroxymethyl)-3,3-dimethyl-1 H,2 H,3 H-pyrrolo[3,2- b]pyridin-1-yl)-2-[(2 R,5 R)-5-methyl-2-([(3R)-3-methylmorpholin-4-yl]methyl)piperazin-1-yl]ethan-1-one (ASTX660).

Inhibitor of apoptosis proteins (IAPs) are promising anticancer targets, given their roles in the evasion of apoptosis. Several peptidomimetic IAP antagonists, with inherent selectivity for cellular IAP (cIAP) over X-linked IAP (XIAP), have been tested in the clinic. A fragment screening approach followed by structure-based optimization has previously been reported that resulted in a low-nanomolar cIAP1 and XIAP antagonist lead molecule with a more balanced cIAP-XIAP profile. We now report the further structure-guided optimization of the lead, with a view to improving the metabolic stability and cardiac safety profile, to give the nonpeptidomimetic antagonist clinical candidate 27 (ASTX660), currently being tested in a phase 1/2 clinical trial (NCT02503423).

ASTX660, a Novel Non-peptidomimetic Antagonist of cIAP1/2 and XIAP, Potently Induces TNFα-Dependent Apoptosis in Cancer Cell Lines and Inhibits Tumor Growth.

Because of their roles in the evasion of apoptosis, inhibitor of apoptosis proteins (IAP) are considered attractive targets for anticancer therapy. Antagonists of these proteins have the potential to switch prosurvival signaling pathways in cancer cells toward cell death. Various SMAC-peptidomimetics with inherent cIAP selectivity have been tested clinically and demonstrated minimal single-agent efficacy. ASTX660 is a potent, non-peptidomimetic antagonist of cIAP1/2 and XIAP, discovered using fragment-based drug design. The antagonism of XIAP and cIAP1 by ASTX660 was demonstrated on purified proteins, cells, and in vivo in xenograft models. The compound binds to the isolated BIR3 domains of both XIAP and cIAP1 with nanomolar potencies. In cells and xenograft tissue, direct antagonism of XIAP was demonstrated by measuring its displacement from caspase-9 or SMAC. Compound-induced proteasomal degradation of cIAP1 and 2, resulting in downstream effects of NIK stabilization and activation of noncanonical NF-κB signaling, demonstrated cIAP1/2 antagonism. Treatment with ASTX660 led to TNFα-dependent induction of apoptosis in various cancer cell lines in vitro, whereas dosing in mice bearing breast and melanoma tumor xenografts inhibited tumor growth. ASTX660 is currently being tested in a phase I-II clinical trial (NCT02503423), and we propose that its antagonism of cIAP1/2 and XIAP may offer improved efficacy over first-generation antagonists that are more cIAP1/2 selective. Mol Cancer Ther; 17(7); 1381-91. ©2018 AACR.

Black phosphorus with near-superhydrophobic properties and long-term stability in aqueous media.

Black phosphorus is a two-dimensional material that has potential applications in energy storage, high frequency electronics and sensing, yet it suffers from instability in oxygenated and/or aqueous systems. Here we present the use of a polymeric stabilizer which prevents the degradation of nearly 68% of the material in aqueous media over the course of ca. 1 month.

Biosynthesis and Characterization of Copper Nanoparticles Using Shewanella oneidensis: Application for Click Chemistry.

Copper nanoparticles (Cu-NPs) have a wide range of applications as heterogeneous catalysts. In this study, a novel green biosynthesis route for producing Cu-NPs using the metal-reducing bacterium, Shewanella oneidensis is demonstrated. Thin section transmission electron microscopy shows that the Cu-NPs are predominantly intracellular and present in a typical size range of 20-40 nm. Serial block-face scanning electron microscopy demonstrates the Cu-NPs are well-dispersed across the 3D structure of the cells. X-ray absorption near-edge spectroscopy and extended X-ray absorption fine-structure spectroscopy analysis show the nanoparticles are Cu(0), however, atomic resolution images and electron energy loss spectroscopy suggest partial oxidation of the surface layer to Cu2 O upon exposure to air. The catalytic activity of the Cu-NPs is demonstrated in an archetypal "click chemistry" reaction, generating good yields during azide-alkyne cycloadditions, most likely catalyzed by the Cu(I) surface layer of the nanoparticles. Furthermore, cytochrome deletion mutants suggest a novel metal reduction system is involved in enzymatic Cu(II) reduction and Cu-NP synthesis, which is not dependent on the Mtr pathway commonly used to reduce other high oxidation state metals in this bacterium. This work demonstrates a novel, simple, green biosynthesis method for producing efficient copper nanoparticle catalysts.

Nanometer Resolution Elemental Mapping in Graphene-Based TEM Liquid Cells.

We demonstrate a new design of graphene liquid cell consisting of a thin lithographically patterned hexagonal boron nitride crystal encapsulated on both sides with graphene windows. The ultrathin window liquid cells produced have precisely controlled volumes and thicknesses and are robust to repeated vacuum cycling. This technology enables exciting new opportunities for liquid cell studies, providing a reliable platform for high resolution transmission electron microscope imaging and spectral mapping. The presence of water was confirmed using electron energy loss spectroscopy (EELS) via the detection of the oxygen K-edge and measuring the thickness of full and empty cells. We demonstrate the imaging capabilities of these liquid cells by tracking the dynamic motion and interactions of small metal nanoparticles with diameters of 0.5-5 nm. We further present an order of magnitude improvement in the analytical capabilities compared to previous liquid cell data with 1 nm spatial resolution elemental mapping achievable for liquid encapsulated bimetallic nanoparticles using energy dispersive X-ray spectroscopy (EDXS).

Discovery of a Potent Nonpeptidomimetic, Small-Molecule Antagonist of Cellular Inhibitor of Apoptosis Protein 1 (cIAP1) and X-Linked Inhibitor of Apoptosis Protein (XIAP).

XIAP and cIAP1 are members of the inhibitor of apoptosis protein (IAP) family and are key regulators of anti-apoptotic and pro-survival signaling pathways. Overexpression of IAPs occurs in various cancers and has been associated with tumor progression and resistance to treatment. Structure-based drug design (SBDD) guided by structural information from X-ray crystallography, computational studies, and NMR solution conformational analysis was successfully applied to a fragment-derived lead resulting in AT-IAP, a potent, orally bioavailable, dual antagonist of XIAP and cIAP1 and a structurally novel chemical probe for IAP biology.

Solution processing of two-dimensional black phosphorus.

Phosphorene, or two-dimensional (2D) black phosphorus (BP) was the first synthetic 2D elemental allotrope beyond graphene to be isolated and studied. It is useful due to its high p-type carrier mobility and direct band gap that is tunable in the range ca. 0.3-2 eV thus bridging the energy gap between graphene and transition metal dichalcogenides such as molybdenum disulfide. Beyond the 'Scotch-Tape' method that was used to isolate the first samples of 2D BP for prototype studies, a range of potentially scalable solution processing techniques emerged later that can produce electronics grade material. This feature article focuses on such solution-process routes to 2D BP and highlights challenges in processing the material, mainly caused by its susceptibility to oxidation, as well as illuminating new avenues and opportunities in the area.

Nanostructured Aptamer-Functionalized Black Phosphorus Sensing Platform for Label-Free Detection of Myoglobin, a Cardiovascular Disease Biomarker.

We report the electrochemical detection of the redox active cardiac biomarker myoglobin (Mb) using aptamer-functionalized black phosphorus nanostructured electrodes by measuring direct electron transfer. The as-synthesized few-layer black phosphorus nanosheets have been functionalized with poly-l-lysine (PLL) to facilitate binding with generated anti-Mb DNA aptamers on nanostructured electrodes. This aptasensor platform has a record-low detection limit (∼0.524 pg mL(-1)) and sensitivity (36 µA pg(-1) mL cm(-2)) toward Mb with a dynamic response range from 1 pg mL(-1) to 16 µg mL(-1) for Mb in serum samples. This strategy opens up avenues to bedside technologies for multiplexed diagnosis of cardiovascular diseases in complex human samples.

Energy Dispersive X-ray Tomography for 3D Elemental Mapping of Individual Nanoparticles.

Energy dispersive X-ray spectroscopy within the scanning transmission electron microscope (STEM) provides accurate elemental analysis with high spatial resolution, and is even capable of providing atomically resolved elemental maps. In this technique, a highly focused electron beam is incident upon a thin sample and the energy of emitted X-rays is measured in order to determine the atomic species of material within the beam path. This elementally sensitive spectroscopy technique can be extended to three dimensional tomographic imaging by acquiring multiple spectrum images with the sample tilted along an axis perpendicular to the electron beam direction. Elemental distributions within single nanoparticles are often important for determining their optical, catalytic and magnetic properties. Techniques such as X-ray tomography and slice and view energy dispersive X-ray mapping in the scanning electron microscope provide elementally sensitive three dimensional imaging but are typically limited to spatial resolutions of > 20 nm. Atom probe tomography provides near atomic resolution but preparing nanoparticle samples for atom probe analysis is often challenging. Thus, elementally sensitive techniques applied within the scanning transmission electron microscope are uniquely placed to study elemental distributions within nanoparticles of dimensions 10-100 nm. Here, energy dispersive X-ray (EDX) spectroscopy within the STEM is applied to investigate the distribution of elements in single AgAu nanoparticles. The surface segregation of both Ag and Au, at different nanoparticle compositions, has been observed.

Sequential bottom-up and top-down processing for the synthesis of transition metal dichalcogenide nanosheets: the case of rhenium disulfide (ReS2).

Bottom-up (aerosol-assisted chemical vapor deposition, AACVD) and top-down (liquid phase exfoliation, LPE) processing methodologies are used in tandem to produce colloids of few-layer thick rhenium disulfide (ReS2) in N-methyl pyrrolidone. The processing route we use is a potentially robust and scalable pathway to manufacture useful 2D materials.

Controlling Size, Morphology, and Surface Composition of AgAu Nanodendrites in 15 s for Improved Environmental Catalysis under Low Metal Loadings.

In this work, a simple but powerful method for controlling the size and surface morphology of AgAu nanodendrites is presented. Control of the number of Ag nanoparticle seeds is found to provide a fast and effective route by which to manipulate the size and morphology of nanoparticles produced via a combined galvanic replacement and reduction reaction. A lower number of Ag nanoparticle seeds leads to larger nanodendrites with the particles' outer diameter being tunable in the range of 45-148 nm. The size and surface morphology of the nanodendrites was found to directly affect their catalytic activity. Specifically, we report on the activity of these AgAu nanodendrites in catalyzing the gas-phase oxidation of benzene, toluene and o-xylene, which is an important reaction for the removal of these toxic compounds from fuels and for environmental remediation. All produced nanodendrite particles were found to be catalytically active, even at low temperatures and low metal loadings. Surprisingly, the largest nanodendrites provided the greatest percent conversion efficiencies.

Tin(II) Sulfide (SnS) Nanosheets by Liquid-Phase Exfoliation of Herzenbergite: IV-VI Main Group Two-Dimensional Atomic Crystals.

The liquid-phase exfoliation of tin(II) sulfide to produce SnS nanosheets in N-methyl-2-pyrrolidone is reported. The material is characterized by Raman spectroscopy, atomic force microscopy, lattice-resolution scanning transmission electron microscope imaging, and energy dispersive X-ray spectrum imaging. Quantum chemical calculations on the optoelectronic characteristics of bulk and 10-layer down to monolayer SnS have been performed using a quantum chemical density functional tight-binding approach. The optical properties of the SnS and centrifugally fractionated SnS nanosheet dispersions were compared to that predicted by theory. Through centrifugation, bilayer SnS nanosheets can be produced size-selectively. The scalable solution processing of semiconductor SnS nanosheets is the key to their commercial exploitation and is potentially an important step toward the realization of a future electronics industry based on two-dimensional materials.

Surface Segregated AgAu Tadpole-Shaped Nanoparticles Synthesized Via a Single Step Combined Galvanic and Citrate Reduction Reaction.

New AgAu tadpole nanocrystals were synthesized in a one-step reaction involving simultaneous galvanic replacement between Ag nanospheres and AuCl4(-)(aq.) and AuCl4(-)(aq.) reduction to Au in the presence of citrate. The AgAu tadpoles display nodular polycrystalline hollow heads, while their undulating tails are single crystals. The unusual morphology suggests an oriented attachment growth mechanism. Remarkably, a 1 nm thick Ag layer was found to segregate so as to cover the entire surface of the tadpoles. By varying the nature of the seeds (Au NPs), double-headed Au tadpoles could also be obtained. The effect of a number of reaction parameters on product morphology were explored, leading to new insights into the growth mechanisms and surface segregation behavior involved in the synthesis of bimetallic and anisotropic nanomaterials.