Preventing SARS-CoV-2 Infection Using Anti-spike Nanobody-IFN-ß Conjugated Exosomes.

PURPOSE: To inhibit the transmission of SARS-CoV-2, we developed engineered exosomes that were conjugated with anti-spike nanobodies and type I interferon ß (IFN-ß). We evaluated the efficacy and potency of nanobody-IFN-ß conjugated exosomes to treatment of SARS-CoV-2 infection. METHODS: Milk fat globule epidermal growth factor 8 (MFG-E8) is a glycoprotein that binds to phosphatidylserine (PS) exposed on the exosomes. We generated nanobody-IFN-ß conjugated exosomes by fusing an anti-spike nanobody and IFN-ß with MFG-E8. We used the SARS-CoV-2 pseudovirus with the spike of the D614G mutant that encodes ZsGreen to mimic the infection process of the SARS-CoV-2. The SARS-CoV-2 pseudovirus was infected with angiotensin-converting enzyme-2 (ACE2) expressing adenocarcinomic human alveolar basal epithelial cells (A549) or ACE2 expressing HEK-blue IFNα/ß cells in the presence of nanobody-IFN-ß conjugated exosomes. By assessing the expression of ZsGreen in target cells and the upregulation of interferon-stimulated genes (ISGs) in infected cells, we evaluated the anti-viral effects of nanobody-IFN-ß conjugated exosomes. RESULTS: We confirmed the anti-spike nanobody and IFN-ß expressions on the exosomes. Exosomes conjugated with nanobody-hIFN-ß inhibited the interaction between the spike protein and ACE2, thereby inhibiting the infection of host cells with SARS-CoV-2 pseudovirus. At the same time, IFN-ß was selectively delivered to SARS-CoV-2 infected cells, resulting in the upregulation of ISGs expression. CONCLUSION: Exosomes conjugated with nanobody-IFN-ß may provide potential benefits in the treatment of COVID-19 because of the cooperative anti-viral effects of the anti-spike nanobody and the IFN-ß.

Detection of SARS-CoV-2 in wastewater in Japan during a COVID-19 outbreak.

The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in wastewater samples has been documented in several countries. Wastewater-based epidemiology (WBE) is potentially effective for early warning of a COVID-19 outbreak. In this study, presence of SARS-CoV-2 RNA in wastewater samples was investigated and was compared with the number of the confirmed COVID-19 cases in the study area during COVID-19 outbreak in Japan. In total, 45 influent wastewater samples were collected from five wastewater treatment plants in Ishikawa and Toyama prefectures in Japan. During the study period, the numbers of confirmed COVID-19 cases in these prefectures increased from 0.3 and 0 to >20 per 100,000 people. SARS-CoV-2 ribonucleic acid (RNA) in the samples was detected using several PCR-based assays. Of the 45 samples, 21 were positive for SARS-CoV-2 according to at least one of the three quantitative RT-PCR assays. The detection frequency increased when the number of total confirmed SARS-CoV-2 cases in 100,000 people exceeded 10 in each prefecture; however, SARS-CoV-2 could also be detected at a low frequency even when the number was below 1.0. SARS-CoV-2 in wastewater could be detected in the early stage of the epidemic, even if the number of confirmed cases potentially underestimates the actual numbers of cases. This suggests that WBE approach can potentially act as an early warning of COVID-19 outbreaks in Japan.

Correction: A silver-manganese dual co-catalyst for selective reduction of carbon dioxide into carbon monoxide over a potassium hexatitanate photocatalyst with water.

Correction for 'A silver-manganese dual co-catalyst for selective reduction of carbon dioxide into carbon monoxide over a potassium hexatitanate photocatalyst with water' by Xing Zhu et al., Chem. Commun., 2019, 55, 13514-13517.

Selective Coupling and Polymerization of Folded Polymer Micelles to Nanodomain Self-Assemblies.

Herein, we developed selective coupling and polymerization systems of folded polymer micelles via physical interaction in water. The polymer micelles serve as nanodomains to provide double core micelles, alternating necklace micelles, and micelle-connected hydrogels. For this, cation- or anion-tail unimer micelles and amine- or carboxy-tail unimer micelles were designed; the unimer micelles consist of folded amphiphilic random copolymers carrying hydrophilic poly(ethylene glycol) and hydrophobic or hydrogen-bonding pendants. Mixing a cation-tail micelle and an anion-tail micelle, and even the combination of a double cation-tail micelle and a double anion-tail micelle, selectively provided double-core micelles in water without forming large aggregates. Double core micelles afforded structural transformation into linear or cyclic polymers and dynamic exchange of the micelle domains. In contrast, mixing amine-tail micelles and carboxy-tail micelles gave an alternating necklace micelle or a hydrogel. The controlled connection of polymer micelles was achieved by designing suitable physical interaction. This technique opened new ways to create various nanodomain self-assemblies with controlled higher-order structure.

A silver-manganese dual co-catalyst for selective reduction of carbon dioxide into carbon monoxide over a potassium hexatitanate photocatalyst with water.

A Ag-Mn dual co-catalyst deposited on a K2Ti6O13 photocatalyst significantly enhances the photocatalytic CO2 reduction into CO with an extremely high selectivity of 98% by using H2O as an electron donor, owing to the properties of Ag and MnOx species for promoting CO and O2 formation, respectively.

Self-Sorting of Amphiphilic Copolymers for Self-Assembled Materials in Water: Polymers Can Recognize Themselves.

Amphiphilic random copolymers bearing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic alkyl pendants showed dynamic self-sorting behavior, that is, self-recognition, under competitive conditions in aqueous media. The self-sorting universally takes place not only in water but also in hydrogels and on the material surfaces, according to encoded information originating from the primary structure of composition and pendants. Binary blends of the copolymers with different composition or alkyl pendants readily induced composition- or alkyl pendant-dependent self-sorting to simultaneously provide discrete and size-controlled micelles with hydrophobic cores. Surprisingly, the micelles reversibly keep exchanging polymer chains exclusively between identical polymer micelles even in the presence of different counterparts. Owing to the dynamic self-sorting behavior, ABA-triblock copolymers comprising the amphiphilic random copolymer A segments and a hydrophilic PEG chain B segment further provided hydrogels with self-healing yet selectively adhesive properties.

Titanium(iv) oxide having a copper co-catalyst: a new type of semihydrogenation photocatalyst working efficiently at an elevated temperature under hydrogen-free and poison-free conditions.

A copper-loaded titanium(iv) oxide photocatalyst exhibited perfect selectivity in hydrogenation of alkynes to alkenes in an alcohol solution at 298 K under hydrogen-free and poison-free conditions. A slight elevation in the reaction temperature to 323 K greatly increased the reaction rate with the selectivity being preserved and the formation of an H2 by-product being suppressed. The apparent activation energy of 4-octyne semihydrogenation was determined to be 54 kJ mol-1, indicating that the rate determining step of this photocatalytic reaction was not an electron production process but a thermocatalytic hydrogenation process under light irradiation.

Effects of neutral salts and pH on the activity and stability of human RNase H2.

Ribonuclease H (RNase H) specifically degrades the RNA of RNA/DNA hybrid. Recent study has shown that a single ribonucleotide is embedded in DNA double strand at every few thousand base pairs in human genome, and human RNase H2 is involved in its removal. Here, we examined the effects of neutral salts and pH on the activity and stability of human RNase H2. NaCl, KCl, RbCl and NaBr increased the activity to 170-390% at 10-60 mM, while LiCl, LiBr and CsCl inhibited it, suggesting that species of cation, but not anion, is responsible for the effect on activity. NaCl and KCl increased the stability by decreasing the first-order rate constant of the inactivation to 50-60% at 60-80 mM. The activity at 25-35 °C exhibited a narrow bell-shaped pH-dependence with the acidic and alkaline pKe (pKe1 and pKe2) values of 7.3 - 7.6 and 8.1 - 8.8, respectively. Enthalpy changes (ΔH°) of deprotonation were 5 ± 21 kJ mol-1 for pKe1 and 68 ± 25 kJ mol-1 for pKe2. These results suggest that the ionizable groups responsible for pKe1 may be two out of Asp34, Glu35 and Asp141 of DEDD motif, and that for pKe2 may be Lys69 of DSK motif.

Experimental and simulation study of undesirable short-period deformation in piezoelectric deformable x-ray mirrors.

To construct adaptive x-ray focusing optics whose optical parameters can be varied while performing wavefront correction, ultraprecise piezoelectric deformable mirrors have been developed. We computationally and experimentally investigated undesirable short-period deformation caused by piezoelectric actuators adhered to the substrate during mirror deformation. Based on the results of finite element method analysis, shape measurements, and the observation of x-ray reflection images, a guideline is developed for designing deformable mirrors that do not have short-period deformation errors.

Wavefield characterization of nearly diffraction-limited focused hard x-ray beam with size less than 10 nm.

In situ wavefront compensation is a promising method to realize a focus size of only a few nanometers for x-ray beams. However, precise compensation requires evaluation of the wavefront with an accuracy much shorter than the wavelength. Here, we characterized a one-dimensionally focused beam with a width of 7 nm at 20 keV using a multilayer mirror. We demonstrate that the wavefront can be determined precisely from multiple intensity profiles measured around the beamwaist. We compare the phase profiles recovered from intensity profiles measured under the same mirror condition but with three different aperture sizes and find that the accuracy of phase retrieval is as small as λ∕12.