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Ellis Hald posted an update 6 days, 22 hours ago
Reports of a cluster of people with pneumonia of unknown etiology surfaced in Wuhan City, China, on December 31, 2019. In early January 2020, the novel coronavirus was isolated and identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the epidemic quickly spread beyond Wuhan City. In the United States, the first case was reported on January 22. By March 1, US cases had increased to 30. After one more month, US cases multiplied drastically to more than 163 000 with almost 3000 dead. On March 11, the World Health Organization declared the outbreak a global pandemic. The disease caused by SARS-CoV-2, COVID-19, proved to be extraordinarily contagious and to cause higher mortality than had previous related viruses; and the death rate is significantly higher among older populations and those with preexisting conditions. Because the current health crisis is caused by the intersection of a virus, preexisting medical conditions, and the social conditions ripe for the virus’s spread and development into severe disease, we recognize this pandemic also as a syndemic.1 (Am J Public Health. Published online ahead of print April 23, 2020 e1-e2. doi10.2105/AJPH.2020.305704).The toxicity of Amphotericin B (AmB) is contributed by the small, water-soluble aggregates of the drug. Hence, AmB lipid polymer hybrid nanoparticles (LIPOMER), comprising stearate lipids with a hydrophilic polymer Gantrez (GZ), and solid lipid nanoparticles (SLN), comprising only stearates, were prepared with the objective of monomerizing AmB. While intercalation of stearates with the hydrophobic polyene chain could hinder AmB-AmB interactions, enabling monomerization, it was hypothesized that GZ could aid in the stabilization of the monomers through hydrophilic interactions. AmB LIPOMERs and SLNs, prepared by nanoprecipitation, exhibited an average size of 350-500 nm with negative ζ potential. Polyglyceryl-6-distearate (PGDS) SLN exhibited maximum monomerization, with the highest peak IV (410 nm) to peak I (350 nm) ratio in the UV-visible spectrum. In total contrast, LIPOMERs and GZ nanoparticles revealed a hypsochromic shifted peak I between 321 and 324 nm, indicative of AmB super-aggregate formation. Super-aggregates, which result due to condensation of multiple aggregates with monomers, were attributed to extensive GZ-AmB and GZ-GZ interactions and could provide advantages of enhanced thermodynamic stability, with safety and efficacy similar to the monomeric form. Safety was confirmed by low and comparable erythrocyte toxicity exhibited by the LIPOMERs and SLNs. An in vitro efficacy study of PGDS LIPOMER and SLN against intracellular amastigotes revealed significantly lower IC50 values, which translated to a 7.1- and 6.1-fold enhancement in efficacy compared to commercial nanoformulations Amfocare (micellar AmB) and 1.79- and 1.54-fold enhancement in efficacy compared to Fungisome (liposomal AmB). High efficacy coupled with a higher selectivity index indicated the superiority of the developed AmB nanoformulations and substantiated that altering the toxic aggregated state of AmB can offer a promising approach for the design of safe and efficacious AmB lipidic nanoformulations.Treatment of 1,n-enynes with gem-dichromiomethane species prepared in situ from 1,1-diiodomethanes and CrCl2 gave alkenylbicycloalkanes. Alkenylcarbene species, which was generated via [2 + 2] cycloaddition with a triple bond, were intercepted by intramolecular cyclopropanation of a pendant double bond, and alkene metathesis did not proceed. This is a very rare example of transformation of alkynyl C≡C with gem-dimetalloalkanes. Silyl- and borylcarbene equivalents generated from gem-(dichromio)silyl- and borylmethanes promoted the coupling and cyclization of enediynes as well as 1,n-enynes.The air-ionic liquid interface for a series of ionic liquids involving imidazolium cations [Cnmim] with different alkyl chain lengths (n = 2, 4, 6, 8, 10, and 12) and the same [NTf2] imide anion has been studied by polarization-resolved second harmonic generation (SHG). An increase as a function of the alkyl chain length of the orientational parameter reveals the increasing ordering of the air-pure ionic liquid interfaces although it is not possible to disentangle the change in mean tilt angle from a change in the tilt angle probability distribution width. Besides, the study of the air-mixed ([C12mim])x([C2mim])1-x[NTf2] ionic liquid interface clearly demonstrates the interfacial nonideality of the mixed ionic liquids. The long alkyl chain cation perturbs the interface as seen from the orientational parameter and displaces the short alkyl chain one for bulk mixture contents as low as 10%. At higher long alkyl chain cation bulk mixture contents, the interface behaves close to a pure long alkyl chain ionic liquid.Sophoraflavanone H (1) is a polyphenol with a hybrid-type structure containing 2,3-diaryl-2,3-dihydrobenzofuran and flavanone ring moieties. This compound and related analogues are promising leads for antimicrobial and antitumor drug development. ARV471 Here we describe a total synthesis of 1 and its diastereomer. The dihydrobenzofuran and flavanone rings were constructed by a Rh-catalyzed asymmetric C-H insertion reaction and selective oxy-Michael reaction. The absolute configuration of 1 was established by X-ray crystallographic analysis and CD spectral investigation of synthetic derivatives.All-dielectric nanoparticle oligomers have recently emerged as promising candidates for nonlinear optical applications. Their highly resonant collective modes, however, are difficult to access by linearly polarized beams due to symmetry restraints. In this paper, we propose a new way to increase the efficiency of nonlinear processes in all-dielectric oligomers by tightly focused azimuthally polarized cylindrical vector beam illumination. We demonstrate two orders enhancement of the third-harmonic generation signal, governed by a collective optical mode represented by out-of-plane magnetic dipoles. Crucially, the collective mode is characterized by strong electromagnetic field localization in the bulk of the nonlinear material. For comparison, we measure third-harmonic generation in the same oligomer pumped with linearly and radially polarized fundamental beams, which both show significantly lower harmonic output. We also provide numerical analysis to describe and characterize the observed effect. Our findings open a new route to enhance and modulate the third-harmonic generation efficiency of Mie-resonant isolated nanostructures by tailoring the polarization of the pump beam.