The novel coronavirus pneumonia (COVID-19) epidemic has brought serious social psychological impact to the Chinese people, especially those quarantined and thus with limited access to face-to-face communication and traditional social psychological interventions. To better deal with the urgent psychological problems of people involved in the COVID-19 epidemic, we developed a new psychological crisis intervention model by utilizing internet technology. This new model, one of West China Hospital, integrates physicians, psychiatrists, psychologists and social workers into Internet platforms to carry out psychological intervention to patients, their families and medical staff. We hope this model will make a sound basis for developing a more comprehensive psychological crisis intervention response system that is applicable for urgent social and psychological problems.

COVID-19 pandemic continues worldwide with many variants arising, especially those of variants of concern (VOCs). A recent VOC, Omicron (B.1.1.529), which obtains a large number of mutations in the receptor-binding domain (RBD) of the spike protein, has risen to intense scientific and public attention. Here we studied the binding properties between the human receptor ACE2 (hACE2) and the VOC RBDs and resolved the crystal and cryo- EM structures of the Omicron RBD-hACE2 complex, as well as the crystal structure of Delta RBD-hACE2 complex. We found that, unlike Alpha, Beta and Gamma, Omicron RBD binds to hACE2 at a similar affinity compared to that of the prototype RBD, which might be due to compensation of multiple mutations for both immune escape and transmissibility. The complex structures of Omicron-hACE2 and Delta-hACE2 reveal the structural basis of how RBD-specific mutations bind to hACE2.

Background The global numbers of confirmed cases and deceased critically ill patients with COVID-19 are increasing. However, the clinical course, and the 60-day mortality and its predictors in critically ill patients have not been fully elucidated. The aim of this study is to identify the clinical course, and 60-day mortality and its predictors in critically ill patients with COVID-19. Methods Critically ill adult patients admitted to intensive care units (ICUs) from 3 hospitals in Wuhan, China, were included. Data on demographic information, preexisting comorbidities, laboratory findings at ICU admission, treatments, clinical outcomes, and results of SARS-CoV-2 RNA tests and of serum SARS-CoV-2 IgM were collected including the duration between symptom onset and negative conversion of SARS-CoV-2 RNA. Results Of 1748 patients with COVID-19, 239 (13.7%) critically ill patients were included. Complications included acute respiratory distress syndrome (ARDS) in 164 (68.6%) patients, coagulopathy in 150 (62.7%) patients, acute cardiac injury in 103 (43.1%) patients, and acute kidney injury (AKI) in 119 (49.8%) patients, which occurred 15.5 days, 17 days, 18.5 days, and 19 days after the symptom onset, respectively. The median duration of the negative conversion of SARS-CoV-2 RNA was 30 (range 6–81) days in 49 critically ill survivors that were identified. A total of 147 (61.5%) patients deceased by 60 days after ICU admission. The median duration between ICU admission and decease was 12 (range 3–36). Cox proportional-hazards regression analysis revealed that age older than 65 years, thrombocytopenia at ICU admission, ARDS, and AKI independently predicted the 60-day mortality. Conclusions Severe complications are common and the 60-day mortality of critically ill patients with COVID-19 is considerably high. The duration of the negative conversion of SARS-CoV-2 RNA and its association with the severity of critically ill patients with COVID-19 should be seriously considered and further studied.

Lipoic acid is synthesized from octanoic acid by insertion of sulfur atoms at carbons 6 and 8 and is covalently attached to a pyruvate dehydrogenase (PDH) subunit. We show that sulfur atoms can be inserted into octanoyl moieties attached to a PDH subunit or a derived domain. Escherichia coli lipB mutants grew well when supplemented with octanoate in place of lipoate. Octanoate growth required both lipoate protein ligase (LplA) and LipA, the sulfur insertion protein, suggesting that LplA attached octanoate to the dehydrogenase and LipA then converted the octanoate to lipoate. This pathway was tested by labeling a PDH domain with deuterated octanoate in an E. coli strain devoid of LipA activity. The labeled octanoyl domain was converted to lipoylated domain upon restoration of LipA. Moreover, octanoyl domain and octanoyl-PDH were substrates for sulfur insertion in vitro.

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Graphical Abstract Highlights d CRISPR screening identified FcRn as an essential and universal EV-B receptor d FcRn facilitates EV-B uncoating and CD55 for attachment d High-resolution Cryo-EM structures described the mechanism of virus entry d The molecular mechanism of dual (attachment versus uncoating) receptor-usage was illustrated SUMMARY a structural basis for understanding the mechanisms of enterovirus entry.

Multiple SARS-CoV-2 variants of concern (VOCs) have been emerging and some have been linked to an increase in case numbers globally. However, there is yet a lack of understanding of the molecular basis for the interactions between the human ACE2 (hACE2) receptor and these VOCs. Here we examined several VOCs including Alpha, Beta, and Gamma, and demonstrate that five variants receptor-binding domain (RBD) increased binding affinity for hACE2, and four variants pseudoviruses increased entry into susceptible cells. Crystal structures of hACE2-RBD complexes help identify the key residues facilitating changes in hACE2 binding affinity. Additionally, soluble hACE2 protein efficiently prevent most of the variants pseudoviruses. Our findings provide important molecular information and may help the development of novel therapeutic and prophylactic agents targeting these emerging mutants.

Lipoic acid is essential for the activation of a number of protein complexes involved in key metabolic processes. Growth of Mycobacterium tuberculosis relies on a pathway in which the lipoate attachment group is synthesized from an endogenously produced octanoic acid moiety. In patients with multiple-drug-resistant M. tuberculosis, expression of one gene from this pathway, lipB, encoding for octanoyl-[acyl carrier protein]-protein acyltransferase is considerably up-regulated, thus making it a potential target in the search for novel antiinfectives against tuberculosis. Here we present the crystal structure of the M. tuberculosis LipB protein at atomic resolution, showing an unexpected thioether-linked activesite complex with decanoic acid. We provide evidence that the transferase functions as a cysteine͞lysine dyad acyltransferase, in which two invariant residues (Lys-142 and Cys-176) are likely to function as acid͞base catalysts. Analysis by MS reveals that the LipB catalytic reaction proceeds by means of an internal thioesteracyl intermediate. Structural comparison of LipB with lipoate protein ligase A indicates that, despite conserved structural and sequence active-site features in the two enzymes, 4-phosphopantetheine-bound octanoic acid recognition is a specific property of LipB.catalytic dyad ͉ lipoic acid ͉ x-ray structure ͉ thioester formation ͉ mass spectrometry S everal multicomponent enzyme complexes that catalyze key metabolic reactions in the citric acid cycle and single-carbon metabolism are posttranslationally modified by attachment to lipoic acid (1). These systems share a domain that covalently binds lipoic acid by means of an amide bond to the -amino group of a conserved exposed lysine residue. In many organisms, lipoylation is catalyzed by two separate enzymes, lipoyl protein ligase A (LplA) or octanoyl-[acyl carrier protein]-protein transferase (LipB; see Fig. 5, which is published as supporting information on the PNAS web site). Although LplA uses exogenous lipoic acid, LipB transfers endogenous octanoic acid, which is attached by means of a thioester bond to the 4Ј-phosphopantetheine cofactor of acyl carrier protein (ACP) onto lipoyl domains (2-4). These octanoylated domains are converted into lipoylated derivatives by the S-adenosyl-L-methioninedependent enzyme, lipoyl synthase (LipA), which catalyzes the insertion of sulfur atoms into the six-and eight-carbon positions of the corresponding fatty acid (5-7). This process bypasses the requirement for an exogenous supply of lipoic acid.In bacteria, enzymes involved in lipoylation have gained increasing attention because of their implication in pathogenicity. For instance, a Listeria monocytogenes mutant strain lacking LplA has been found to be defective in its ability to grow in the host cytosol and is less virulent in animals because of its dependence on host-derived lipoic acid (8). Mice Lias Ϫ/Ϫ (LipA) null variants die during embryogenesis, indicating that the mammalian pathway is related to the bacterial LipB͞LipA pathway and is essenti...