Medical imaging is routine in the diagnosis and staging of a wide range of medical conditions. In particular, magnetic resonance imaging (MRI) is critical for visualizing soft tissue and organs, with ...over 60 million MRI procedures performed each year worldwide. About one-third of these procedures are contrast-enhanced MRI, and gadolinium-based contrast agents (GBCAs) are the mainstream MRI contrast agents used in the clinic. GBCAs have shown efficacy and are safe to use with most patients; however, some GBCAs have a small risk of adverse effects, including nephrogenic systemic fibrosis (NSF), the untreatable condition recently linked to gadolinium (Gd) exposure during MRI with contrast. In addition, Gd deposition in the human brain has been reported following contrast, and this is now under investigation by the US Food and Drug Administration (FDA). To address a perceived need for a Gd-free contrast agent with pharmacokinetic and imaging properties comparable to GBCAs, we have designed and developed zwitterion-coated exceedingly small superparamagnetic iron oxide nanoparticles (ZES-SPIONs) consisting of ∼3-nm inorganic cores and ∼1-nm ultrathin hydrophilic shell. These ZES-SPIONs are free of Gd and show a high T₁ contrast power. We demonstrate the potential of ZES-SPIONs in preclinical MRI and magnetic resonance angiography.
Ligands are essential for controlling the reactivity and selectivity of reactions catalysed by transition metals. Access to large phosphine ligand libraries has become an essential tool for the ...application of metal-catalysed reactions industrially, but these existing libraries are not well suited to new catalytic methods based on non-precious metals (for example, Ni, Cu and Fe). The development of the requisite nitrogen- and oxygen-based ligand libraries lags far behind that of the phosphines and the development of new libraries is anticipated to be time consuming. Here we show that this process can be dramatically accelerated by mining for new ligands in a typical pharmaceutical compound library that is rich in heterocycles. Using this approach, we were able to screen a structurally diverse set of compounds with minimal synthetic effort and identify several new ligand classes for nickel-catalysed cross-electrophile coupling. These new ligands gave improved yields for challenging cross-couplings of pharmaceutically relevant substrates compared with those of those of previously published ligands.
Stabilization of the crystal phase of inorganic/organic lead halide perovskites is critical for their high performance optoelectronic devices. However, due to the highly ionic nature of perovskite ...crystals, even phase stabilized polycrystalline perovskites can undergo undesirable phase transitions when exposed to a destabilizing environment. While various surface passivating agents have been developed to improve the device performance of perovskite solar cells, conventional deposition methods using a protic polar solvent, mainly isopropyl alcohol (IPA), results in a destabilization of the underlying perovskite layer and an undesirable degradation of device properties. We demonstrate the hidden role of IPA in surface treatments and develop a strategy in which the passivating agent is deposited without destabilizing the high quality perovskite underlayer. This strategy maximizes and stabilizes device performance by suppressing the formation of the perovskite δ-phase and amorphous phase during surface treatment, which is observed using conventional methods. Our strategy also effectively passivates surface and grain boundary defects, minimizing non-radiative recombination sites, and preventing carrier quenching at the perovskite interface. This results in an open-circuit-voltage loss of only ∼340 mV, a champion device with a power conversion efficiency of 23.4% from a reverse current-voltage scan, a device with a record certified stabilized PCE of 22.6%, and enhanced operational stability. In addition, our perovskite solar cell exhibits an electroluminescence external quantum efficiency up to 8.9%.
Newly developed passivation strategy results in unprecedented perovskite optoelectronic device performances.
β-Mannans are plant cell wall polysaccharides that are commonly found in human diets. However, a mechanistic understanding into the key populations that degrade this glycan is absent, especially for ...the dominant Firmicutes phylum. Here, we show that the prominent butyrate-producing Firmicute Roseburia intestinalis expresses two loci conferring metabolism of β-mannans. We combine multi-"omic" analyses and detailed biochemical studies to comprehensively characterize loci-encoded proteins that are involved in β-mannan capturing, importation, de-branching and degradation into monosaccharides. In mixed cultures, R. intestinalis shares the available β-mannan with Bacteroides ovatus, demonstrating that the apparatus allows coexistence in a competitive environment. In murine experiments, β-mannan selectively promotes beneficial gut bacteria, exemplified by increased R. intestinalis, and reduction of mucus-degraders. Our findings highlight that R. intestinalis is a primary degrader of this dietary fiber and that this metabolic capacity could be exploited to selectively promote key members of the healthy microbiota using β-mannan-based therapeutic interventions.
Despite their importance, the synthesis of alkylated heterocycles from the cross-coupling of Lewis basic nitrogen heteroaryl halides with alkyl halides remains a challenge. We report here a general ...solution to this challenge enabled by a new collection of ligands based around 2-pyridyl-N-cyanocarboxamidine and 2-pyridylcarboxamidine cores. Both primary and secondary alkyl halides can be coupled with 2-, 3-, and 4-pyridyl halides as well as other more complex heterocycles in generally good yields (41 examples, 69% ave yield).
The bacterial domain produces numerous types of sphingolipids with various physiological functions. In the human microbiome, commensal and pathogenic bacteria use these lipids to modulate the host ...inflammatory system. Despite their growing importance, their biosynthetic pathway remains undefined since several key eukaryotic ceramide synthesis enzymes have no bacterial homolog. Here we used genomic and biochemical approaches to identify six proteins comprising the complete pathway for bacterial ceramide synthesis. Bioinformatic analyses revealed the widespread potential for bacterial ceramide synthesis leading to our discovery of a Gram-positive species that produces ceramides. Biochemical evidence demonstrated that the bacterial pathway operates in a different order from that in eukaryotes. Furthermore, phylogenetic analyses support the hypothesis that the bacterial and eukaryotic ceramide pathways evolved independently.
While the evidence is clear that 2020 voters shifted away from Election Day voting in favor of vote-by-mail and early voting, we know very little about how health risk versus party polarization ...around risk assessment influenced how and when to vote. We rely on individual-level observational data in the form of high-quality official voter administrative records from the State of New Mexico to ask how pandemic-related risk factors, especially voter age along with partisanship influenced voter decision-making. To identify causal factors, we use a difference-in-differences design and hazard model that compare 2020 general election and primary voter behavior to 2018 and 2016. We find that age and party were large factors in vote mode decisions in 2020, but not in 2016 or 2018. We consider the implications of our findings on how health risk and partisanship interact to influence decision-making.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
While reductive cross-electrochemical coupling is an attractive approach for the synthesis of complex molecules at both small and large scale, two barriers for large-scale applications have remained: ...the use of stoichiometric metal reductants and a need for amide solvents. In this communication, new conditions that address these challenges are reported. The nickel-catalyzed reductive cross-coupling of aryl bromides with alkyl bromides can be conducted in a divided electrochemical cell using acetonitrile as the solvent and diisopropylamine as the sacrificial reductant to afford coupling products in synthetically useful yields (22–80%). Additionally, the use of a combination of the ligands 4,4′,4″-tri-tert-butyl-2,2′:6′,2′-terpyridine and 4,4′-di-tert-butyl-2,2′-bipyridine is essential to achieve high yields.
The Giant Gartersnake (Thamnophis gigas) is a low density visually evasive species with a low detection probability based on standard field survey methods (e.g., traps, visual census). Habitat loss ...has resulted in extirpations or serious declines for T. gigas populations throughout the southern two thirds of its historic range. Uncertainty regarding its current distribution and occupancy present management challenges for the species. Enhancing survey sensitivity through development of environmental DNA sampling (eDNA) methods would improve compliance monitoring under the Endangered Species Act, recovery planning for T. gigas, and evaluation of California's Central Valley tule marsh habitat on which this species depends. To address these needs, we designed and validated diagnostic quantitative Polymerase Chain Reaction (qPCR) assays for identifying portions of the Cytochrome B (CytB) and the Nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 4 (ND4) genes of the T. gigas mitochondrial genome. The designed ND4 qPCR assay was not specific to T. gigas DNA and amplified DNA from a closely related and spatially co-occurring Thamnophis species (T.s. fitchi). The CytB T. gigas qPCR assay proved specific to a species level with a sensitivity that reliably detected T. gigas DNA at a concentration of 2.0x10-5 ng μL-1. To assess detection range, coordinated field sampling was conducted at aquatic sites with an observed and documented population of T. gigas. The T. gigas qPCR assay reliably detected DNA from samples taken 300m downstream from the known source. We then used environmental eDNA sampling and qPCR analysis to augment unsuccessful trap surveys in the southern range of T. gigas and detected DNA in 28 of the 52 locations sampled, confirming that T. gigas was still present at some sites where physical trapping failed to identify presence. QPCR-based DNA detection coupled with eDNA sampling methods provides an effective means to obtain critical population metrics from this otherwise cryptic, federally protected and hard to study organism, offering great promise for elucidating patterns of occupancy with greater efficiency and at far less cost than trapping methods, particularly where detection probabilities are low.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Next-generation optoelectronic applications centered in the near-infrared (NIR) and short-wave infrared (SWIR) wavelength regimes require high-quality materials. Among these materials, colloidal InAs ...quantum dots (QDs) stand out as an infrared-active candidate material for biological imaging, lighting, and sensing applications. Despite significant development of their optical properties, the synthesis of InAs QDs still routinely relies on hazardous, commercially unavailable precursors. Herein, we describe a straightforward single hot injection procedure revolving around In(I)Cl as the key precursor. Acting as a simultaneous reducing agent and In source, In(I)Cl smoothly reacts with a tris(amino)arsenic precursor to yield colloidal InAs quantitatively and at gram scale. Tuning the reaction temperature produces InAs cores with a first excitonic absorption feature in the range of 700–1400 nm. A dynamic disproportionation equilibrium between In(I), In metal, and In(III) opens up additional flexibility in precursor selection. CdSe shell growth on the produced cores enhances their optical properties, furnishing particles with center emission wavelengths between 1000 and 1500 nm and narrow photoluminescence full-width at half-maximum (FWHM) of about 120 meV throughout. The simplicity, scalability, and tunability of the disclosed precursor platform are anticipated to inspire further research on In-based colloidal QDs.
PDF
