From the beginning of 2002 and 2012, severe respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) crossed the species barriers to infect humans, causing thousands of infections and hundreds of deaths, respectively. Currently, a novel coronavirus (SARS-CoV-2), which has become the cause of the outbreak of Coronavirus Disease 2019 (COVID-19), was discovered. Until 18 February 2020, there were 72 533 confirmed COVID-19 cases (including 10 644 severe cases) and 1872 deaths in China. SARS-CoV-2 is spreading among the public and causing substantial burden due to its human-to-human transmission. However, the intermediate host of SARS-CoV-2 is still unclear. Finding the possible intermediate host of SARS-CoV-2is imperative to prevent further spread of the epidemic. In this study, we used systematic comparison and analysis to predict the interaction between the receptor-binding domain (RBD) of coronavirus spike protein and the host receptor, angiotensin-converting enzyme 2 (ACE2). The interaction between the key amino acids of S protein RBD and ACE2 indicated that, other than pangolins and snakes, as previously suggested, turtles (Chrysemys picta bellii, Chelonia mydas, and Pelodiscus sinensis) may act as the potential intermediate hosts transmitting SARS-CoV-2 to humans.

The regulation of stomatal lineage cell development has been extensively investigated. However a comprehensive characterization of this biological process based on single-cell transcriptome analysis has not yet been reported. Here, we performed RNA-seq on over 12,844 individual cells from the cotyledons of five-day-old Arabidopsis seedlings. We identified 11 cell clusters corresponding mostly to cells at specific stomatal developmental stages with a series of new marker genes. Comparative analysis of genes with the highest variable expression in these cell clusters revealed three transcriptional networks that regulate the development of mesophyll and guard cells, as well as the differentiation from protodermal to guard mother cells. We investigated the developmental dynamics of marker genes via pseudo-time analysis which revealed potential interactions between them. The identification of several novel marker genes suggests new regulatory mechanisms during development of stomatal cell lineage. .

Hyperhomocysteinemia (HHcy) is a risk factor for various cardiovascular diseases. However, the mechanism underlying HHcy-aggravated vascular injury remains unclear. Here we show that the aggravation of abdominal aortic aneurysm by HHcy is abolished in mice with genetic deletion of the angiotensin II type 1 (AT1) receptor and in mice treated with an AT1 blocker. We find that homocysteine directly activates AT1 receptor signalling. Homocysteine displaces angiotensin II and limits its binding to AT1 receptor. Bioluminescence resonance energy transfer analysis reveals distinct conformational changes of AT1 receptor upon binding to angiotensin II and homocysteine. Molecular dynamics and site-directed mutagenesis experiments suggest that homocysteine regulates the conformation of the AT1 receptor both orthosterically and allosterically by forming a salt bridge and a disulfide bond with its Arg167 and Cys289 residues, respectively. Together, these findings suggest that strategies aimed at blocking the AT1 receptor may mitigate HHcy-associated aneurysmal vascular injuries.

A mid-infrared spectroscopic method was developed for the simultaneous and quantitative determination of total protein, carbohydrate and lipid contents of microalgal cells. Based on a chemometric approach, measured FTIR (Fourier transform infrared) spectra from algal cells were reconstructed by a partial least square algorithm, using the spectra of the reference substances to determine their relative contribution to the overall cell spectrum. From this specific absorption, absolute macromolecular cell composition [pg cell(-1)] can be calculated using calibration curves, which have been validated by independent biochemical methods. The future potential of this method for photosynthesis research is shown by its application to follow time-resolved changes in the cellular composition of microalgae during an illumination period of several hours. We show how the macromolecular composition can be investigated by FTIR spectroscopy methods. This can substantially increase the efficiency of screening processes like bioreactor monitoring and may be beneficial in metabolic engineering of algal cells.

Seven transmembrane G protein-coupled receptors (GPCRs) are often phosphorylated at the C terminus and on intracellular loops in response to various extracellular stimuli. Phosphorylation of GPCRs by GPCR kinases and certain other kinases can promote the recruitment of arrestin molecules. The arrestins critically regulate GPCR functions not only by mediating receptor desensitization and internalization, but also by redirecting signaling to G protein-independent pathways via interactions with numerous downstream effector molecules. Accumulating evidence over the past decade has given rise to the phospho-barcode hypothesis, which states that ligand-specific phosphorylation patterns of a receptor direct its distinct functional outcomes. Our recent work using unnatural amino acid incorporation and fluorine-19 nuclear magnetic resonance (F-NMR) spectroscopy led to the flute model, which provides preliminary insight into the receptor phospho-coding mechanism, by which receptor phosphorylation patterns are recognized by an array of phosphate-binding pockets on arrestin and are translated into distinct conformations. These selective conformations are recognized by various effector molecules downstream of arrestin. The phospho-barcoding mechanism enables arrestin to recognize a wide range of phosphorylation patterns of GPCRs, contributing to their diverse functions.

ObjectivesTo determine whether humour therapy reduces depression (primary outcome), agitation and behavioural disturbances and improves social engagement and quality-of-life in nursing home residents.DesignThe Sydney Multisite Intervention of LaughterBosses and ElderClowns study was a single-blind cluster randomised controlled trial of humour therapy.Setting35 Sydney nursing homes.ParticipantsAll eligible residents within geographically defined areas within each nursing home were invited to participate.InterventionProfessional ‘ElderClowns’ provided 9–12 weekly humour therapy sessions, augmented by resident engagement by trained staff ‘LaughterBosses’. Controls received usual care.MeasurementsDepression scores on the Cornell Scale for Depression in Dementia, agitation scores on the Cohen-Mansfield Agitation Inventory, behavioural disturbance scores on the Neuropsychiatric Inventory, social engagement scores on the withdrawal subscale of Multidimensional Observation Scale for Elderly Subjects, and self-rated and proxy-rated quality-of-life scores on a health-related quality-of-life tool for dementia, the DEMQOL. All outcomes were measured at the participant level by researchers blind to group assignment.RandomisationSites were stratified by size and level of care then assigned to group using a random number generator.ResultsSeventeen nursing homes (189 residents) received the intervention and 18 homes (209 residents) received usual care. Groups did not differ significantly over time on the primary outcome of depression, or on behavioural disturbances other than agitation, social engagement and quality of life. The secondary outcome of agitation was significantly reduced in the intervention group compared with controls over 26 weeks (time by group interaction adjusted for covariates: p=0.011). The mean difference in change from baseline to 26 weeks in Blom-transformed agitation scores after adjustment for covariates was 0.17 (95% CI 0.004 to 0.34, p=0.045).ConclusionsHumour therapy did not significantly reduce depression but significantly reduced agitation.Trial registrationAustralian New Zealand Clinical Trials Registry -ACTRN12611000462987.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the third most common coronavirus that causes large-scale infections worldwide. The correlations between pathogen susceptibility and blood type distribution have attracted attention decades ago. The current retrospective study aimed to examine the correlation between blood type distribution and SARS-CoV-2 infection, progression, and prognosis in patients with coronavirus disease 2019 . With 265 patients from multiple medical centers and two established cohorts, we found that the blood type A population was more sensitive to SARS-CoV-2. Moreover, the blood type distribution was not relevant to acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and mortality in COVID-19 patients. These findings are indicative of coping with the great threat since it probed the relationship between blood types and ARDS, AKI, and mortality, in addition to susceptibility in COVID-19 patients.

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