Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a newly emerging human infectious disease. Because no specific antiviral drugs or vaccines are available to treat COVID-19, early diagnostics, isolation, and prevention are crucial for containing the outbreak. Molecular diagnostics using reverse transcription polymerase chain reaction (RT-PCR) are the current gold standard for detection. However, viral RNAs are much less stable during transport and storage than proteins such as antigens and antibodies. Consequently, false-negative RT-PCR results can occur due to inadequate collection of clinical specimens or poor handling of a specimen during testing. Although antigen immunoassays are stable diagnostics for detection of past infection, infection progress, and transmission dynamics, no matched antibody pair for immunoassay of SARS-CoV-2 antigens has yet been reported. In this study, we designed and developed a novel rapid detection method for SARS-CoV-2 spike 1 (S1) protein using the SARS-CoV-2 receptor ACE2, which can form matched pairs with commercially available antibodies. ACE2 and S1-mAb were paired with each other for capture and detection in a lateral flow immunoassay (LFIA) that did not cross-react with SARS-CoV Spike 1 or MERS-CoV Spike 1 protein. The SARS-CoV-2 S1 (<5 ng of recombinant proteins/reaction) was detected by the ACE2-based LFIA. The limit of detection of our ACE2-LFIA was 1.86 × 10 5 copies/mL in the clinical specimen of COVID-19 Patients without no cross-reactivity for nasal swabs from healthy subjects. This is the first study to detect SARS-CoV-2 S1 antigen using an LFIA with matched pair consisting of ACE2 and antibody. Our findings will be helpful to detect the S1 antigen of SARS-CoV-2 from COVID-19 patients.

Lee et al. find that phospholipase D2 deficiency increases survival and decreases organ damage during experimental sepsis in mice which could be reversed with a CXCR2 antagonist. Thus, targeting PLD2 may offer therapeutics for septic patients.

Highlights d Psychological stress triggers vaso-occlusive episodes (VOEs) in sickle cell disease d Stress-induced VOEs depend on the microbiota d The stress response is enabled by the hypothalamicpituitary-adrenal axis d Stress-induced VOEs are mediated by aged neutrophil expansion via the IL-17/G-CSF pathway

Transforming growth factor (TGF)-b, a pivotal cytokine involved in a variety of cellular functions, transmits signals through Smad-dependent canonical and Smad-independent noncanonical pathways. In contrast to the canonical TGF-b pathway, it is unknown how noncanonical TGF-b pathways are negatively regulated. Here we demonstrate that the inhibitory Smad Smad6, but not Smad7, negatively regulates TGF-b1-induced activation of the TRAF6-TAK1-p38 MAPK/JNK pathway, a noncanonical TGF-b pathway. TGF-b1-induced Smad6 abolishes K63-linked polyubiquitination of TRAF6 by recruiting the A20 deubiquitinating enzyme in AML-12 mouse liver cells and primary hepatocytes. In addition, the knockdown of Smad6 or A20 in an animal model or cell culture system maintains TAK1 and p38 MAPK/JNK phosphorylation and increases apoptosis, emphasizing the crucial role of the Smad6-A20 axis in negative regulation of the TGF-b1-TRAF6-TAK1-p38 MAPK/JNK pathway. Therefore, our findings provide insight into the molecular mechanisms underlying negative regulation of noncanonical TGF-b pathways.

Large-scale fabrication of platinum (Pt) nanoshell tubes has been accomplished via a simple and convenient method:  porous templates are wetted at ambient conditions with a polymer/Pt precursor solution. Annealing yields functionalized membranes having Pt-coated pore walls. Unsupported Pt nanoshell tubes are accessible by selectively removing the template. We have also synthesized composite tubes having an outer Pt shell and an inner polymer core by performing consecutive wetting steps. The tube diameter is adjustable by using templates with respective pore diameters. We demonstrate that “giant” nanoshell tubes with a diameter of 1 μm can be fabricated. They exhibit nanostructured walls consisting of sintered crystallites extending approximately 10 nm and can thus be considered as a hierarchical system combining nano- and microscale features.