The coronavirus disease 2019 (COVID-19) pandemic poses a current world-wide public health threat. However, little is known about its hallmarks compared to other infectious diseases. Here, we report ...the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19- and influenza A virus (IAV)-infected patients. We observed increase of plasma cells in both COVID-19 and IAV patients and XIAP associated factor 1 (XAF1)-, tumor necrosis factor (TNF)-, and FAS-induced T cell apoptosis in COVID-19 patients. Further analyses revealed distinct signaling pathways activated in COVID-19 (STAT1 and IRF3) versus IAV (STAT3 and NFκB) patients and substantial differences in the expression of key factors. These factors include relatively increase of interleukin (IL)6R and IL6ST expression in COVID-19 patients but similarly increased IL-6 concentrations compared to IAV patients, supporting the clinical observations of increased proinflammatory cytokines in COVID-19 patients. Thus, we provide the landscape of PBMCs and unveil distinct immune response pathways in COVID-19 and IAV patients.
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•We generated a single-cell atlas of PBMCs in both COVID-19 and influenza patients•Plasma cells increase significantly in both COVID-19 and influenza patients•COVID-19 is featured with XAF1-, TNF-, and FAS-induced T cell apoptosis•COVID-19 activates distinct pathway (STAT1/IRF3) versus influenza (STAT3/NFκB)
COVID-19 and influenza are both respiratory infections with cytokine release syndrome. Zhu et al. use single-cell RNA sequencing of longitudinally collected PBMCs in both patients to reveal distinct immune response landscapes of the two diseases and identify virus-specific cell composition and immune response pathways.
Glassy polyimide membranes are attractive for industrial applications in sour natural gas purification. Unfortunately, the lack of fundamental understanding of relationships between polyimide ...chemical structures and their gas transport properties in the presence of H2S constrains the design and engineering of advanced membranes for such challenging applications. Herein, 6FDA‐based polyimide membranes with engineered structures were synthesized to tune their CO2/CH4 and H2S/CH4 separation performances and plasticization properties. Under ternary mixed sour gas feeds, controlling polymer chain packing and plasticization tendency of such polyimide membranes via tuning the chemical structures were found to offer better combined H2S and CO2 removal efficiency compared to conventional polymers. Fundamental insights into structure–property relationships of 6FDA‐based polyimide membranes observed in this study offer guidance for next generation membranes for sour natural gas separation.
No need to be sour: CO2/CH4 and H2S/CH4 separation performance of glassy polyimide membranes can be tailored by finely tuning the DAM:DABA ratio in the 6FDA‐DAM:DABA polyimide backbone. This facile tunability is attractive for their applications for challenging sour gas separation (that is, methane contaminated with undesirable acid gases (CO2 and H2S)) across a spectrum of feed compositions.
We have surveyed avian influenza virus (AIV) genomes from live poultry markets within China since 2014. Here we present a total of 16,091 samples that were collected from May 2016 to February 2019 in ...23 provinces and municipalities in China. We identify 2048 AIV-positive samples and perform next generation sequencing. AIV-positive rates (12.73%) from samples had decreased substantially since 2016, compared to that during 2014-2016 (26.90%). Additionally, H9N2 has replaced H5N6 and H7N9 as the dominant AIV subtype in both chickens and ducks. Notably, novel reassortants and variants continually emerged and disseminated in avian populations, including H7N3, H9N9, H9N6 and H5N6 variants. Importantly, almost all of the H9 AIVs and many H7N9 and H6N2 strains prefer human-type receptors, posing an increased risk for human infections. In summary, our nation-wide surveillance highlights substantial changes in the circulation of AIVs since 2016, which greatly impacts the prevention and control of AIVs in China and worldwide.
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 has generated enormous interest in the ...biodiversity, genomics and cross-species transmission potential of coronaviruses, especially those from bats, the second most speciose order of mammals. Herein, we identified a novel coronavirus, provisionally designated Rousettus bat coronavirus GCCDC1 (Ro-BatCoV GCCDC1), in the rectal swab samples of Rousettus leschenaulti bats by using pan-coronavirus RT-PCR and next-generation sequencing. Although the virus is similar to Rousettus bat coronavirus HKU9 (Ro-BatCoV HKU9) in genome characteristics, it is sufficiently distinct to be classified as a new species according to the criteria defined by the International Committee of Taxonomy of Viruses (ICTV). More striking was that Ro-BatCoV GCCDC1 contained a unique gene integrated into the 3'-end of the genome that has no homologs in any known coronavirus, but which sequence and phylogeny analyses indicated most likely originated from the p10 gene of a bat orthoreovirus. Subgenomic mRNA and cellular-level observations demonstrated that the p10 gene is functional and induces the formation of cell syncytia. Therefore, here we report a putative heterologous inter-family recombination event between a single-stranded, positive-sense RNA virus and a double-stranded segmented RNA virus, providing insights into the fundamental mechanisms of viral evolution.
Abstract
A recent outbreak of pneumonia in Wuhan, China was found to be caused by a 2019 novel coronavirus (2019-nCoV or SARS-CoV-2 or HCoV-19). We previously reported the clinical features of 12 ...patients with 2019-nCoV infections in Shenzhen, China. To further understand the pathogenesis of COVID-19 and find better ways to monitor and treat the disease caused by 2019-nCoV, we measured the levels of 48 cytokines in the blood plasma of those 12 COVID-19 patients. Thirty-eight out of the 48 measured cytokines in the plasma of 2019-nCoV-infected patients were significantly elevated compared to healthy individuals. Seventeen cytokines were linked to 2019-nCoV loads. Fifteen cytokines, namely M-CSF, IL-10, IFN-α2, IL-17, IL-4, IP-10, IL-7, IL-1ra, G-CSF, IL-12, IFN-γ, IL-1α, IL-2, HGF and PDGF-BB, were strongly associated with the lung-injury Murray score and could be used to predict the disease severity of 2019-nCoV infections by calculating the area under the curve of the receiver-operating characteristics. Our results suggest that 2019-nCoV infections trigger extensive changes in a wide array of cytokines, some of which could be potential biomarkers of disease severity of 2019-nCoV infections. These findings will likely improve our understanding of the immunopathologic mechanisms of this emerging disease. Our results also suggest that modulators of cytokine responses may play a therapeutic role in combating the disease once the functions of these elevated cytokines have been characterized.
Avian-origin influenza viruses overcome the bottleneck of the interspecies barrier and infect humans through the evolution of variants toward more efficient replication in mammals. The dynamic ...adaptation of the genetic substitutions and the correlation with the virulence of avian-origin influenza virus in patients remain largely elusive. Here, based on the one-health approach, we retrieved the original virus-positive samples from patients with H7N9 and their surrounding poultry/environment. The specimens were directly deep sequenced, and the subsequent big data were integrated with the clinical manifestations. Unlike poultry/environment-derived samples with the consistent dominance of avian signature 627E of H7N9 polymerase basic protein 2 (PB2), patient specimens had diverse ratios of mammalian signature 627K, indicating the rapid dynamics of H7N9 adaptation in patients during the infection process. In contrast, both human- and poultry/environment-related viruses had constant dominance of avian signature PB2-701D. The intrahost dynamic adaptation was confirmed by the gradual replacement of 627E by 627K in H7N9 in the longitudinally collected specimens from one patient. These results suggest that host adaptation for better virus replication to new hosts, termed “genetic tuning,” actually occurred in H7N9-infected patients in vivo. Notably, our findings also demonstrate the correlation between rapid host adaptation of H7N9 PB2-E627K and the fatal outcome and disease severity in humans. The feature of H7N9 genetic tuning in vivo and its correlation with the disease severity emphasize the importance of testing for the evolution of this avian-origin virus during the course of infection.
Membrane‐based gas separations are energy efficient processes; however, major challenges remain to develop high‐performance membranes enabling the replacement of conventional separation processes. ...Herein, a new fluorinated MOF‐based mixed‐matrix membrane is reported, which is formed by incorporating the MOF crystals into selected polymers via a facile mixed‐matrix approach. By finely controlling the molecular transport in the channels through the MOF apertures tuned by metal pillars and at the MOF‐polymer interfaces, the resulting fluorinated MOF‐based membranes exhibit excellent molecular sieving properties. These materials significantly outperform state‐of‐the‐art membranes for simultaneous removal of H2S and CO2 from natural gas—a challenging and economically important application. The robust fluorinated MOFs (NbOFFIVE‐1‐Ni, AlFFIVE‐1‐Ni), pave a way to efficient membrane separation processes that require precise discrimination of closely sized molecules.
Separate ways: New fluorinated metal–organic framework (MOF)‐based mixed‐matrix membranes with finely controlled molecular transport in the channels through the MOF aperture exhibit excellent molecular‐sieving properties that significantly outperform state‐of‐the‐art membranes for simultaneous removal of H2S and CO2 from natural gas.
NAD is an obligate co-factor for the catabolism of metabolic fuels in all cell types. However, the availability of NAD in several tissues can become limited during genotoxic stress and the course of ...natural aging. The point at which NAD restriction imposes functional limitations on tissue physiology remains unknown. We examined this question in murine skeletal muscle by specifically depleting Nampt, an essential enzyme in the NAD salvage pathway. Knockout mice exhibited a dramatic 85% decline in intramuscular NAD content, accompanied by fiber degeneration and progressive loss of both muscle strength and treadmill endurance. Administration of the NAD precursor nicotinamide riboside rapidly ameliorated functional deficits and restored muscle mass despite having only a modest effect on the intramuscular NAD pool. Additionally, lifelong overexpression of Nampt preserved muscle NAD levels and exercise capacity in aged mice, supporting a critical role for tissue-autonomous NAD homeostasis in maintaining muscle mass and function.
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•Mice with ∼85% NAD depletion in skeletal muscle are grossly normal as young adults•Reduced NAD content impairs mitochondrial function and fiber integrity over time•Progressive muscle dysfunction can be reversed by the NAD precursor NR•Preventing muscle NAD loss during aging partially preserves exercise performance
NAD levels decline in multiple tissues with age or in disease. Frederick et al. show that impaired intramuscular NAD synthesis compromises skeletal muscle mass and strength over time but can be quickly restored with an oral NAD precursor. Upregulation of the NAD salvage pathway preserves exercise performance in aged mice.
Rings are the most frequently revealed substructure in Atacama Large Millimeter/submillimeter Array (ALMA) dust observations of protoplanetary disks, but their origin is still hotly debated. In this ...paper, we identify dust substructures in 12 disks and measure their properties to investigate how they form. This subsample of disks is selected from a high-resolution (∼0 12) ALMA 1.33 mm survey of 32 disks in the Taurus star-forming region, which was designed to cover a wide range of brightness and to be unbiased to previously known substructures. While axisymmetric rings and gaps are common within our sample, spiral patterns and high-contrast azimuthal asymmetries are not detected. Fits of disk models to the visibilities lead to estimates of the location and shape of gaps and rings, the flux in each disk component, and the size of the disk. The dust substructures occur across a wide range of stellar mass and disk brightness. Disks with multiple rings tend to be more massive and more extended. The correlation between gap locations and widths, the intensity contrast between rings and gaps, and the separations of rings and gaps could all be explained if most gaps are opened by low-mass planets (super-Earths and Neptunes) in the condition of low disk turbulence ( = 10−4). The gap locations are not well correlated with the expected locations of CO and N2 ice lines, so condensation fronts are unlikely to be a universal mechanism to create gaps and rings, though they may play a role in some cases.
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