Identification of a novel astrovirus from intestinal tissue of a donkey foal with severe diarrhea in China

DEAR EDITOR,Astroviruses are known to cause gastroenteritis and diarrhea symptoms in various hosts.However,no information is currently available on any donkey astrovirus genome.In this study,we collected six intestinal samples from donkey foals that died of severe diarrhea on a donkey farm in Shandong Province,China,in 2021.Based on metagenomic nextgeneration sequencing,a nearly complete donkey astrovirus 1(DAstV-1)sequence was detected as the only possible diarrhea-related mammalian virus.

Virome in healthy pangolins reveals compatibility with multiple potentially zoonotic viruses

Previous studies have identified multiple viruses in dead or severely diseased pangolins,but descriptions of the virome in healthy pangolins are lacking.This poses a greater risk of cross-species transmission due to poor preventive awareness and frequent interactions with breeders.In this study,we investigated the viral composition of 34 pangolins with no signs of disease at the time of sampling and characterized a large number of arthropodassociated viruses belonging to 11 families and vertebrate viruses belonging to eight families,including those with pathogenic potential in humans and animals.Several important vertebrate viruses were identified in the pangolins,including parvovirus,pestivirus,and picobirnavirus.The picobirnavirus was clustered with human and grey teal picobirnaviruses.Viruses with cross-species transmission ability were also identified,including circovirus,rotavirus,and astrovirus.Our study revealed that pangolins are frequently exposed to arthropod-associated viruses in the wild and can carry many vertebrate viruses under natural conditions.This study provides important insights into the virome of pangolins,underscoring the importance of monitoring potential pathogens in healthy pangolins to prevent outbreaks of infectious diseases in domesticated animals and humans.

Advances in oxidative stress and NOD-like/toll-like receptors in acute renal injury

Acute Kidney Injury(AKI)is a clinical syndrome characterized by rapid renal deterioration with high morbidity and mortality.Renal reperfusion(IRI),renal toxicity and sepsis are the main causes of AKI.IRI is one of the main causes of acute kidney injury in clinic,accounting for 75%of all the causes of AKI[1].The fatality rate of AKI caused by IRI is high,and the surviving patients may leave chronic renal impairment with different degrees[2].A number of studies have shown that ischemia-reperfusion injury leading to renal dysfunction is directly related to oxidative stress,and the inhibition of oxidative stress through nod-like/toll-like signaling pathway can reduce acute renal injury.This review summarizes the research progress in regulating oxidative stress and the relationship between innate immune receptors and acute renal injury.

A novel flotation scheme: selective flotation of tungsten minerals from calcium minerals using Pb–BHA complexes in Shizhuyuan

The similar floatabilities of calcium minerals and the huge difference between scheelite and wolframite have resulted in difficulties during their separation by flotation in Shizhuyuan Mine. In this study, novel collectors, lead complexes of benzohydroxamic acid（Pb-BHA）,were introduced to modify the surface properties of scheelite and wolframite, thereby effectively and selectively improving floatability. The Pb-BHA complexes are found to be selective for the separation of scheelite and calcium minerals with little use of depressants and enable the synchronous flotation of scheelite and wolframite.Hence, a novel flotation process was developed for the recovery of tungsten minerals. The process is simplified greatly, and the recovery is improved by almost 10%.Removing or decreasing the amount of water glass contributes to the improvement of tungsten and fluorite recovery and the circulation of water and reagents, which benefits the environment.

Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus-related coronavirus model

Background:Medicines for the treatment of 2019-novel coronavirus(2019-nCoV)infections are urgently needed.However,drug screening using live 2019-nCoV requires high-level biosafety facilities,which imposes an obstacle for those institutions without such facilities or 2019-nCoV.This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019(COVID-19)in a 2019-nCoV-related coronavirus model.Methods:A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described.Whether GX_P2V uses angiotensin-converting enzyme 2(ACE2)as the cell receptor was investigated by using small interfering RNA(siRNA)-mediated silencing of ACE2.The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection.Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection.The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated.Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction(qRT-PCR)and plaque assay,respectively.Results:The spike protein of coronavirus GX_P2V shares 92.2%amino acid identity with that of 2019-nCoV isolate Wuhanhu-1,and uses ACE2 as the receptor for infection just like 2019-nCoV.Three drugs,including cepharanthine(CEP),selamectin,and mefloquine hydrochloride,exhibited complete inhibition of cytopathic effects in cell culture at 10μmol/L.CEP demonstrated the most potent inhibition of GX_P2V infection,with a concentration for 50%of maximal effect[EC50]of 0.98μmol/L.The viral RNA yield in cells treated with 10μmol/L CEP was 15,393-fold lower than in cells without CEP treatment([6.48±0.02]×10-4vs.1.00±0.12,t=150.38,P<0.001)at 72 h post-infection(p.i.).Plaque assays found no production of live viruses in media containing 10μmol/L CEP at 48 h p.i.Furthermore,we found CEP had potent anti-viral activities against both viral entry(0.46±0.12,vs.1.00±0.37,t=2.42,P<0.05)and viral replication([6.18±0.95]×10-4vs.1.00±0.43,t=3.98,P<0.05).Conclusions:Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research.CEP,selamectin,and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection.Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus,and further study of CEP for treatment of 2019-nCoV infection is warranted.

An important mechanism of herb-induced hepatotoxicity: To produce RMs based on active functional groups-containing ingredients from phytomedicine by binding CYP450s

Reactive metabolites(RMs) generated by hepatic metabolism are thought to play an important role in the pathogenesis of drug-induced liver injury(DILI). Like many synthetic drugs undergoing metabolic activation to form RMs which are often associated with drug toxicity, it is recognized that some herbal components may be also converted to toxic, or even mutagenetic and carcinogenic metabolites by cytochrome P450 s(CYP450 s). This review focuses on the metabolic activation of herbal components and its liver toxicological implications. By summarizing references, we found that hepatotoxic herbal components via producing RMs have some certain structural dependence. There is a correlation between the generation of RMs and the structures, which provides a good chance for the early discovery of toxic ingredients in Traditional Chinese medicines(TCMs): i) A potential hepatotoxic component information database based on active functional groups can be built, which might provide an early information for the basic research of hepatotoxic substances in TCMs;ii) RMs can combine with CYP450 s to form a complete antigen, which eventually leads to an antigen-specific immune response. RMs-CYP450 protein complete antigen can be set up, and the potential idiosyncratic liver toxicity might be predicted by testing RMs-CYP450 protein antibody in plasma.