Chicken or Porcine Aminopeptidase N Mediates Cellular Entry of Pseudoviruses Carrying Spike Glycoprotein from the Avian Deltacoronaviruses HKU11, HKU13, and HKU17.

Members of deltacoronavirus (DCoV) have mostly been identified in diverse avian species as natural reservoirs, though the porcine DCoV (PDCoV) is a major swine enteropathogenic virus with global spread. The important role of aminopeptidase N (APN) orthologues from various mammalian and avian species in PDCoV cellular entry and interspecies transmission has been revealed recently. In this study, comparative analysis indicated that three avian DCoVs, bulbul DCoV HKU11, munia DCoV HKU13, and sparrow DCoV HKU17 (Chinese strain), and PDCoV in the subgenera Buldecovirus are grouped together at whole-genome levels; however, the spike (S) glycoprotein and its S1 subunit of HKU17 are more closely related to night heron DCoV HKU19 in Herdecovirus. Nevertheless, the S1 protein of HKU11, HKU13, or HKU17 bound to or interacted with chicken APN (chAPN) or porcine APN (pAPN) by flow cytometry analysis of cell surface expression of APN and by coimmunoprecipitation in APN-overexpressing cells. Expression of chAPN or pAPN allowed entry of pseudotyped lentiviruses with the S proteins from HKU11, HKU13 and HKU17 into nonsusceptible cells and natural avian and porcine cells, which could be inhibited by the antibody against APN or anti-PDCoV-S1. APN knockdown by siRNA or knockout by CRISPR/Cas9 in chicken or swine cell lines significantly or almost completely blocked infection of these pseudoviruses. Hence, we demonstrate that HKU11, HKU13, and HKU17 with divergent S genes likely engage chAPN or pAPN to enter the cells, suggesting a potential interspecies transmission from wild birds to poultry and from birds to mammals by certain avian DCoVs. IMPORTANCE The receptor usage of avian deltacoronaviruses (DCoVs) has not been investigated thus far, though porcine deltacoronavirus (PDCoV) has been shown to utilize aminopeptidase N (APN) as a cell receptor. We report here that chicken or porcine APN also mediates cellular entry by three avian DCoV (HKU11, HKU13, and HKU17) spike pseudoviruses, and the S1 subunit of three avian DCoVs binds to APN in vitro and in the surface of avian and porcine cells. The results fill the gaps in knowledge about the avian DCoV receptor and elucidate important insights for the monitoring and prevention of potential interspecies transmission of certain avian DCoVs. In view of the diversity of DCoVs, whether this coronavirus genus will cause novel virus to emerge in other mammals from birds, are worthy of further surveillance and investigation.

Clinical efficacy analysis of butylphthalide combined with urinary kallidinogenase in treating chronic cerebral circulatory insufficiency.

OBJECTIVE: To investigate the clinical effect of butylphthalide combined with urinary kallidinogenase in the treatment of chronic cerebral circulatory insufficiency (CCCI). METHODS: A total of 102 CCCI patients admitted to our hospital from October 2020 to December 2021 were retrospectively enrolled in this study. According to the different therapeutic strategy, the patients were divided into combined group (treated with butylphthalide combined with urinary kallidinogenase, n = 51) and butylphthalide group (treated with butylphthalide, n = 51). Blood flow velocity and cerebral blood flow perfusion before and after treatment between the two groups were compared. The clinical efficacy and adverse events of the two groups were analyzed. RESULTS: After treatment, the effective rate of the combined group was significantly higher than the butylphthalide group (p = .015). Before treatment, the blood flow velocity of middle cerebral artery (MCA), vertebral artery (VA), basilar artery (BA) were comparable (p > .05, respectively), while after treatment, the blood flow velocity of MCA, VA, and BA in combined group were faster than those in butylphthalide group (p < .001, respectively). Before treatment, the relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), relative mean transmit time (rMTT) of the two groups were comparable (p > .05, respectively). After treatment, rCBF and rCBV in combined group were higher than those in butylphthalide group (p < .001, respectively), and rMTT in combined group was lower than that in butylphthalide group (p = .001). The rate of adverse events in the two groups were comparable (p = .558). CONCLUSION: Butylphthalide combined with urinary kallidinogenase can improve the clinical symptoms of CCCI patients, and the effect is promising, which is worthy of clinical application.

Light-Activated Fuel-Free Janus Metal Organic Framework Colloidal Motors for the Removal of Heavy Metal Ions.

Light-powered fuel-free colloidal motors possess significant potential for practical applications ranging from nanomedicine to environmental remediation. However, current light-powered colloidal motors often require the incorporation of expensive metals or high concentrations of toxic chemical fuels, which is a severe limitation for their practical applications. Integrating highly ordered and porous materials with a large surface area into colloidal motors is a promising strategy for upsurging their self-propelled speed and adsorption, which will benefit many applications. Here, highly efficient, fuel-free, and light-activated metal organic framework (MOF)-3-trimethoxysilyl propyl methacrylate Janus colloidal motors with a hierarchical morphology are reported. These colloidal motors can be driven by UV or visible light, with a self-propelled speed tuned by the light intensity. The speed can be further enhanced by morphology optimization or by the addition of H2O2 as a fuel. The colloidal motors display a superior efficiency in removing heavy metal ions of Hg, which is up to ∼90% within 40 min from the contaminated water, attributed to their high surface area, hierarchical morphology, large number of active sites, and high mobility. This work not only offers a facile approach to incorporate a versatile MOF family into the design of fuel-free and light-powered Janus colloidal motors, but also demonstrates their potential for real-life applications such as environmental remediation.

Effect of Alkalinity on Catalytic Activity of Iron-Manganese Co-Oxide in Removing Ammonium and Manganese: Performance and Mechanism.

In this study, a pilot-scale experimental filter system was used to investigate the effect of bicarbonate alkalinity on the activity of an Fe-Mn co-oxide for ammonium and manganese removal from surface water. The results showed that an increase in alkalinity to 150 mg/L (calculated as CaCO3) by the addition of NaHCO3 significantly promoted the activity of the Fe-Mn co-oxide. The ammonium and manganese removal efficiencies of the Fe-Mn co-oxide increased from 40% to 95% and 85% to 100%, respectively. After NaHCO3 was no longer added, the activity of the filter column remained. Moreover, pH (7.4-8.0) and temperature (12.0-16.0 °C) were not the main factors affecting the activity of the filter, and had no significant effect on the activity of the filter. Further characterization analysis of the Fe-Mn co-oxide filter film showed that after alkalinity was increased, the accumulation of aluminum on the filter media surface decreased from 3.55% to 0.16% and the oxide functional groups changed. This was due to the action of bicarbonate and the residual aluminum salt coagulant in the filter, which caused the loss of Al from the surface of the filter media and weakened the influence of the aluminum salt coagulant on the activity of the Fe-Mn co-oxide; hence, the activity was recovered.