Amorphous calcium carbonate plays a key role as transient precursor in the early stages of biogenic calcium carbonate formation in nature. However, due to its instability in aqueous solution, there is still rare success to utilize amorphous calcium carbonate in biomedicine. Here, we report the mutual effect between paramagnetic gadolinium ions and amorphous calcium carbonate, resulting in ultrafine paramagnetic amorphous carbonate nanoclusters in the presence of both gadolinium occluded highly hydrated carbonate-like environment and poly(acrylic acid). Gadolinium is confirmed to enhance the water content in amorphous calcium carbonate, and the high water content of amorphous carbonate nanoclusters contributes to the much enhanced magnetic resonance imaging contrast efficiency compared with commercially available gadolinium-based contrast agents. Furthermore, the enhanced T1 weighted magnetic resonance imaging performance and biocompatibility of amorphous carbonate nanoclusters are further evaluated in various animals including rat, rabbit and beagle dog, in combination with promising safety in vivo. Overall, exceptionally facile mass-productive amorphous carbonate nanoclusters exhibit superb imaging performance and impressive stability, which provides a promising strategy to design magnetic resonance contrast agent.
Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is currently a global pandemic, and there is a lack of laboratory studies targeting pathogen resistance.Objective To investigate the effect of selected disinfection products and methods on the inactivation of SARS-CoV-2.Methods We used quantitative suspension testing to evaluate the effectiveness of the disinfectant/method.Results Available chlorine of 250 mg/L, 500 mg/L, and 1000 mg/L required 20 min, 5 min, and 0.5 min to efficiently inactivate SARS-CoV-2, respectively. A 600-fold dilution of 17% concentration of di-N-decyldimethylammonium bromide (283 mg/L) and the same concentration of di-N-decyldimethylammonium chloride required only 0.5 min to efficiently inactivate the virus. Ethanol, at 30% concentration for 1 min, and 40% and above for 0.5 min, could efficiently inactivate SARS-CoV-2. Heat takes approximate 30 min at 56°C, or 10 min above 70°C, or 5 min above 90°C to inactivate the virus.Conclusions The chlorinated disinfectants, Di-N-decyldimethylammonium bromide / chloride, ethanol, and heat were effective in inactivating SARS-CoV-2. The response of SARS-CoV-2 to disinfectants is very similar to that of SARS-CoV.
Inspired by the biosynthesis of heparan sulfate (HS), we present adirectepimerization approachtol-iduronic acid synthons (IdoA) from the corresponding C5 epimers, d-glucuronic acids (GlcA). With the best result, 95 % conversion was achieved.Weak intramolecular interactions dramatically affect the equilibrium constants of this thermodynamically governed process. Based on this approach, GlcA and IdoA donors required for the synthesis of fondaparinux were prepared in 14 steps, whereas over 20 steps were required previously.Heparan sulfate (HS) oligosaccharides act as ligands for numerous proteins, thusregulating an assortment of biological activities [1] that can be probedbysynthesized HS with defined structures. However,H Ss ynthesis is ad aunting task. For instance, it required around 60 steps [2] to preparet he pentasaccharideH S drug fondaparinux (Figure 1) in aS anofip atent.C onsiderable efforts have thus been taken recently to develop new strategies and methods for HS synthesis.[3] Notable advances include a-glucosaminylation methods, [4] modular synthetic approaches, [5] one-pot synthesis, [6] chemoenzymatic synthesis, [7] and others. Structurally,H Sc onsists of N-glucosamine and hexuronic acid units, specifically either GlcA or its C5 epimer IdoA. One lasting challenge in HS synthesis is the preparation of the IdoA synthon. While IdoA is biosynthesized via C5 epimerizationo f GlcA in ao ne-step, base-catalyzed process, [8] traditional chemical synthetic routes have been quite laborious. These multistep routes involve redox manipulations [9] or nucleophilic substitution of C5-activated precursors.[5b ,c 10] Herein, ab iomimetic chemicala pproachi sd escribed, which can provide both IdoA and GlcA donors in ac onvergent route.The investigation was initiated by attempting as eries of C5 epimerization reactions using 0.5 m NaOMe in anhydrous methanol( Scheme 1). NMR analysiso ft he neutralized reaction samples indicated that abeta-thiophenyl donor of unprotected glucuronide (S1)o ri ts amide derivative (S2)y ieldedl ittle IdoA products.I nc ontrast, the ester S3 was convertedi nto its C5 epimer S3-IdoA with the molar ratio of S3 to S3-IdoA slowly climbing to 1:1w ithin 24 h. Similarc onditions were previously used to prepare l-IdoA glycal derivatives, [11] which unfortunately could not be efficientlyc onverted into IdoA synthons. [9i] In an effort to improve the conversions een with S3-IdoA, six more GlcA substrates were prepared (Figure 2). All substratesc ontained am ethyl ester at the C6 positiong iven the resultsa bove, and the C4 functionality wasl eft as af ree hydroxy group to avoid b-elimination.C onsistent with previous HS syntheses, [2, 3] the substituent at the C3 position, which is Scheme1.C5-epimerizationo ft hreeGlcA derivatives.[a] X.
Amorphous calcium carbonate (ACC) plays a key role as transient precursor in the early stages of biogenic calcium carbonate formation in nature. However, due to its instability in aqueous solution, there is still rare success to utilize ACC in biomedicine. Here, we report the mutual effect between paramagnetic gadolinium ions and ACC, resulting in ultrafine paramagnetic amorphous carbonate nanoclusters (ACNC) in the presence of both gadolinium occluded highly hydrated ACC-like environment and poly(acrylic acid). Gadolinium is confirmed to enhance the water content in ACC, and the high water content of ACNC (23 molecules H2O per 1 Gd) contributes to the much enhanced magnetic resonance imaging (MRI) contrast efficiency compared with commercially available gadolinium-based contrast agents. Furthermore, the enhanced T1 weighted MRI performance and biocompatibility of ACNC are further evaluated in various animals including rat, rabbit and beagle dog, in combination with promising safety in vivo. Overall, exceptionally facile mass-productive ACNC exhibits superb imaging performance and impressive stability, which provides a promising strategy to design MR contrast agents.
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