There is a rapidly expanding literature on the in vitro antiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against SARS-CoV-2. However, this has not been accompanied by a comprehensive evaluation of the target plasma and lung concentrations of these drugs following approved dosing in humans. Accordingly, EC90 values recalculated from in vitro anti-SARS-CoV-2 activity data was expressed as a ratio to the achievable maximum plasma concentrations (Cmax) at an approved dose in humans (Cmax/EC90 ratio). Only 14 of the 56 analysed drugs achieved a Cmax/EC90 ratio above 1. A more in-depth assessment demonstrated that only nitazoxanide, nelfinavir, tipranavir (ritonavir-boosted) and sulfadoxine achieved plasma concentrations above their reported anti-SARS-CoV-2 activity across their entire approved dosing interval. An unbound lung to plasma tissue partition coefficient (Kp Ulung ) was also simulated to derive a lung Cmax/EC50 as a better indicator of potential human efficacy. Hydroxychloroquine, chloroquine, mefloquine, atazanavir (ritonavir-boosted), tipranavir (ritonavir-boosted), ivermectin, azithromycin and lopinavir (ritonavir-boosted) were all predicted to achieve lung concentrations over 10-fold higher than their reported EC50 . Nitazoxanide and sulfadoxine also exceeded their reported EC50 by 7.8- and 1.5-fold in lung, respectively. This analysis may be used to select potential candidates for further clinical testing, while deprioritising compounds unlikely to attain target concentrations for antiviral activity. Future studies should focus on EC90 values and discuss findings in the context of achievable exposures in humans, especially within target compartments such as the lung, in order to maximise the potential for success of proposed human clinical trials.Antibiotics have adverse effects on human health and aquatic ecosystems in water environment, which is the main pool. In this study, antibiotics in the aquatic environment of China, containing both surface water and groundwater, were first systematically reviewed. That is essential for surface water and groundwater guideline and industry management. 128 articles were reviewed, containing 116 papers on surface water and 12 papers on groundwater. 94 antibiotics were detected at least once in the aquatic environment of China and most of the studies were in the eastern areas of China. Poziotinib nmr The median concentrations of most antibiotics were below than 100 ng/L in the surface water and 10 ng/L in the groundwater. The concentrations of most antibiotics in China were similar or a little higher than in other countries. According to risk assessment, three antibiotics (enrofloxacin, ofloxacin and erythromycin) and three regions (Haihe River, Wangyang River and Taihu Lake) should be given more concerns. Strengthened policy and management are needed in these regions. In the future, more studies on groundwater and a priority list of antibiotics in the aquatic environment was needed.We read with interest your recent article by Fogarty et al, in particular their conclusion that differences in thrombotic risk may contribute to ethnic disparities in mortality from Covid-19.(1) This is especially important in the UK, where age-sex adjusted hospital death rates for Covid-19 are 2.17 times higher for people with ethnicity recorded as black compared to those recorded as white, and 1.95 higher for those recorded as Asian.(2) This excess mortality persists after adjustment for deprivation, body mass index (BMI), smoking and comorbidities,(2) and despite correction for region, rural or urban living, deprivation, household composition, socioeconomic status, and health.(3) Similar data from the USA shows that in 14 states, African-Americans represent 33% of hospitalisations for Covid-19, despite only making up 14% of the catchment population.(4) Black ethnicity is a construct incorporating diverse populations of African descent. Studies from several communities labelled as black, in particular African-Americans, imply a common increase in thrombotic risk, which may contribute to unexplained ethnic disparities in the UK and USA in Covid-19.Filamentous fungi are important industrial cell factories used for the production of a wide range of enzymes and metabolites. Their primary metabolism is a significant source of industrially important compounds, as well as of monomeric building blocks for the production of secondary metabolites and extracellular enzymes. Therefore, large efforts have been made towards the development of suitable strains for the industrial scale production of primary metabolites. Over the last decades, metabolic engineering of primary metabolism has become a powerful tool to enhance production of both primary and secondary metabolites. This review summarises the different metabolic engineering methods that have been applied to rationally improve the production of industrially relevant primary metabolites in filamentous fungi, and discusses related challenges and future perspectives.Background Liver enzyme abnormality is common in patients with coronavirus disease 2019 (COVID-19). Whether or not SARS-CoV-2 infection can lead to liver damage per se remains unknown. Here we reported the clinical characteristics and liver pathological manifestations of COVID-19 patients with liver enzyme abnormality. Methods We received 156 patients diagnosed of COVID-19 from two designated centers in China, and compared clinical features between patients with elevated aminotransferase or not. Postmortem liver biopsies were obtained from two cases who had elevated aminotransferase. We investigated the patterns of liver impairment by electron microscopy, immunohistochemistry, TUNEL assay, and pathological studies. Results 64 of 156 (41.0%) COVID-19 patients had elevated aminotransferase. The median levels of ALT were 50 U/L vs. 19 U/L, respectively, AST were 45.5 U/L vs. 24 U/L, respectively in abnormal and normal aminotransferase groups. The liver enzyme abnormality was associated with disease severity, as 9 is required.Hypothalamic stimulation can elicit complex behaviors such as aggression, but how discrete motor components of such behaviors are organized at the circuit level remains largely unknown. In this issue of Neuron, Falkner et al. (2020) find that complex neural representations get transformed into a simplified action signal along a hypothalamic-midbrain pathway.