Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and ...subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis.
We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and compared virus tropism and replication competence with SARS-CoV, Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung (n=4). We assessed extrapulmonary infection using ex-vivo cultures of human conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell lines. Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. In-vitro studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and mock-infected cells as controls.
SARS-CoV-2 infected ciliated, mucus-secreting, and club cells of bronchial epithelium, type 1 pneumocytes in the lung, and the conjunctival mucosa. In the bronchus, SARS-CoV-2 replication competence was similar to MERS-CoV, and higher than SARS-CoV, but lower than H1N1pdm. In the lung, SARS-CoV-2 replication was similar to SARS-CoV and H1N1pdm, but was lower than MERS-CoV. In conjunctiva, SARS-CoV-2 replication was greater than SARS-CoV. SARS-CoV-2 was a less potent inducer of proinflammatory cytokines than H5N1, H1N1pdm, or MERS-CoV.
The conjunctival epithelium and conducting airways appear to be potential portals of infection for SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium; SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV. These findings provide important insights into the transmissibility and pathogenesis of SARS-CoV-2 infection and differences with other respiratory pathogens.
US National Institute of Allergy and Infectious Diseases, University Grants Committee of Hong Kong Special Administrative Region, China; Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong Special Administrative Region, China.
The Notch pathway contributes to self-renewal of tumor-initiating cell and inhibition of normal colonic epithelial cell differentiation. Deregulated expression of Notch1 and Jagged1 is observed in ...colorectal cancer. Hairy/enhancer of split (HES) family, the most characterized targets of Notch, involved in the development of many cancers. In this study, we explored the role of Hes1 in the tumorigenesis of colorectal cancer. Knocking down Hes1 induced CRC cell senescence and decreased the invasion ability, whereas over-expression of Hes1 increased STAT3 phosphorylation activity and up-regulated MMP14 protein level. We further explored the expression of Hes1 in human colorectal cancer and found high Hes1 mRNA expression is associated with poor prognosis in CRC patients. These findings suggest that Hes1 regulates the invasion ability through the STAT3-MMP14 pathway in CRC cells and high Hes1 expression is a predictor of poor prognosis of CRC.
The aim of this study was to chemically characterize the fine particulate matter (PM2.5) at a subtropical forest in East Asia under the influences of anthropogenic and biogenic sources and a complex ...topographic setting. Four seasonal campaigns were conducted at the Xitou Experimental Forest in central Taiwan from the winter of 2013 to the autumn of 2014. The results indicated that the ambient levels and chemical features of PM2.5 exhibited pronounced seasonal variations. Non-sea-salt sulfate (nss-SO42-) constituted the major component of PM2.5, followed by ammonium (NH4+) and nitrate (NO3−) during winter, summer and autumn. However, it was revealed that the mass fraction of NO3− increased to be comparable with that of nss-SO42- in springtime. The mass contribution of secondary organic carbon (SOC) to PM2.5 peaked in summer (13.2%), inferring the importance of enhanced photo-oxidation reactions in SOC formation. Diurnal variations of O3 and SO2 coincided with each other, suggesting the transport of aged pollutants from distant sources, whereas CO and NOx were shown to be under the influences of both local and regional sources. Notably high sulfur oxidation ratio (SOR) and nitrogen oxidation ratio (NOR) were observed, which were 0.93 ± 0.05 and 0.39 ± 0.20, respectively. Precursor gases (i.e. SO2 and NOx) could be converted to sulfate and nitrate during the transport by the uphill winds. Furthermore, due to the high relative humidity at Xitou, enhanced aqueous-phase and/or heterogeneous reactions could further contribute to the formation of sulfate and nitrate at the site. This study demonstrated the significant transport of urban pollutants to a subtropical forest by the mountain-valley circulations as well as the long-range transport from regional sources, whereas the implications of which for regional climate change necessitated further investigation.
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•Distinct seasonal variations are observed in PM2.5 composition at forest site.•Notably high nitrate concentrations (6.19 μg/m3) are found in spring.•Significant secondary organic carbon (up to13.2% in summer) in PM2.5•The sulfur and nitrogen oxidation ratios are 0.93 and 0.39
Four measurement campaigns were conducted at Xitou Experimental Forest in central Taiwan to characterize the fine particulate matter (PM2.5) at a high-elevation subtropical forest in East Asia where pollutants were effectively transported by mountain-valley circulations, and long-range transport from regional sources.
Abstract
Transport and transformation of urban air pollutants are among the major factors driving the changes in the atmospheric composition in the downwind rural/remote areas of a megacity. Here, we ...assess the impacts of urban air pollution in a subtropical forest through characterization of the organic markers in submicron aerosol particles. The aerosol samples were collected and analyzed using TD-PTR-ToF-MS, where 163 ions were detected. The concentration of these extracted ions accounts for 83% of the mass of submicron organic aerosols, which are accordingly characterized by a median formula of C
7
H
10
O
2
. Molecular speciation indicates that urban and biomass burning pollution contributed substantially to the budget of organic aerosols, which were enhanced particularly by the liquid water content and acidity of the aerosols. Our results evidence that the footprint of urban air pollution was extended to its downwind forested areas and caused changes in the concentration and composition of submicron aerosols.
Summary
Background
It has been suggested that beta‐blockers may increase mortality in patients with cirrhosis and refractory ascites but the effect of beta‐blockers discontinuation or reinitiation ...has not been examined.
Aims
To compare, in hospitalised patients with cirrhosis and ascites, the effect of BB on survival and to examine the effect/predictors of beta‐blockers discontinuation and reinitiation.
Methods
Sub‐analysis of NACSELD (North American consortium for the study of end‐stage liver disease, database containing prospective data on hospitalised patients with cirrhosis) data from 7 centres enrolling >100 patients with ascites. Data on BB discontinuation and reinitiation were collected by chart review.
Results
Seven hundred and sixteen patients, 307 (43%) on beta‐blockers at admission and 366 (51%) with refractory ascites, were followed to death or hospital discharge. Beta‐blocker use was associated with a lower white blood cell count at admission. Beta‐blocker use in hospitalised patients with ascites was not associated with a higher mortality, even in those with refractory ascites. No significant changes in mean arterial pressure (MAP) were observed between groups. Discontinuation of beta‐blockers (49%) was driven by low MAP, infection and acute kidney injury at time of discontinuation but was not associated with a higher mortality. Beta‐blocker reinitiation occurred in 40% prior to discharge and was mainly driven by an increase in MAP.
Conclusions
Beta‐blocker use is safe in patients with cirrhosis and ascites (including those with refractory ascites) provided beta‐blockers are discontinued in the presence of a low MAP and reinitiated once MAP reincreases. A potentially beneficial anti‐inflammatory effect of beta‐blockers is suggested.
Linked ContentThis article is linked to Ferguson and Armstrong paper. To view this article visit https://doi.org/10.1111/apt.14402.
The oxygen evolution reaction (OER) is the half reaction in the overall reaction of electrocatalytic water splitting, and it involves four electron transfers. The aforementioned electron requirement ...implies that the OER requires more energy than the HER, thus limiting the overall water splitting efficiency. Here, we propose a novel anode catalyst by using an advanced composite material of selenized nickel–iron electrodes together with NiFe_LDH. An analysis of the water splitting performance was carried out in different concentrations of a seawater-like electrolyte, which, in terms of corrosion reactions, is a relatively harsher environment than that found in natural seawater. In this study, we discovered that a Se_NiFe foam electrode with an LDH layer exhibited extraordinary stability and activity in an aqueous sea-like solution, demonstrating an improved overpotential from the original 1.62 V–1.43 V in a seawater electrolyte mixture. Furthermore, the Tafel slope significantly decreased from 115.1 mV dec−1 to 26.3 mV dec−1. Notably, the lifespan of this novel electrode was extended from 80 h to 250 h. The mechanism of improved stability and corrosion resistance is also investigated in this study.
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•Oxygen can be selectively and stably generated in seawater-like solution with cheap electrode materials and electrode architecture.•Selenized nickel–iron electrodes with the selenide layer possessed good conductivity and corrosion resistance.•The NiFe–LDH layer on the electrodes surface, which can effectively reduce overpotential and improve corrosion.•This study successfully demonstrated the lifespan of this novel electrode was extended upto 250 h for industrial application.
Organonitrates (ONs) are an important component of atmospheric aerosols that signify the perturbation of nitrogen oxides (NOx) pollution in the remote atmosphere. This study investigated the mass ...concentration and molecular composition of ONs in submicron particulate matters (PM1) at a subtropical forest site (Xitou), which located downwind the Taichung metropolis in the Central Taiwan. Here we showed that transport of urban air pollution with local circulations caused elevation in the ambient concentration of ONs in the forested area. In addition, the levels of ONs were positively correlated with ozone mixing ratio and were negatively correlated with the relative humidity, suggesting that the ONs were regulated by photochemistry and hydrolysis. The results also showed that the mass concentration of the ONs was significantly correlated with the number density of nanoparticles (d < 100 nm), implying the role of ONs in the formation and/or growth processes of atmospheric aerosols. Mass spectra analysis revealed five major ONs, which were characterized by the molecular skeletons of either isoprene or monoterpenes. The molecular profiles suggested that the reactions between nitrate radicals and biogenic volatile organic compounds (BVOCs) significantly contributed to the formation of ONs, which thereby represented a major sink of the functional BVOCs in the forested area.
•Both the mass concentration and the molecular identity of particulate organonitrates were determined using a TD-PTR-TOF-MS.•Photochemistry and hydrolysis dictated the mass concentration of organonitrates•Nitrate (NO3) initiated oxidation of BVOCs participated in the formation of organonitrates in daytime•NOx pollution enhanced formation of organonitrates and the sink of functional BVOCs in a forested area
We report four previously undescribed families with germline BRCA1‐associated protein‐1 gene (BAP1) mutations and expand the clinical phenotype of this tumor syndrome. The tumor spectrum in these ...families is predominantly uveal malignant melanoma (UMM), cutaneous malignant melanoma (CMM) and mesothelioma, as previously reported for germline BAP1 mutations. However, mutation carriers from three new families, and one previously reported family, developed basal cell carcinoma (BCC), thus suggesting inclusion of BCC in the phenotypic spectrum of the BAP1 tumor syndrome. This notion is supported by the finding of loss of BAP1 protein expression by immunochemistry in two BCCs from individuals with germline BAP1 mutations and no loss of BAP1 staining in 53 of sporadic BCCs consistent with somatic mutations and loss of heterozygosity of the gene in the BCCs occurring in mutation carriers. Lastly, we identify the first reported recurrent mutation in BAP1 (p.R60X), which occurred in three families from two different continents. In two of the families, the mutation was inherited from a common founder but it arose independently in the third family.
In this study, we investigated the biodegradation of the phthalate acid esters (PAEs) di-
n-butyl phthalate (DBP) and di-(2-ethyl hexyl) phthalate (DEHP) in compost and compost-amended soil. DBP (50
...mg
kg
−1) and DEHP (50
mg
kg
−1) were added to the two types of compost (straw and animal manure) and subsequently added to the soil; they were tested as a single compound and in combination. Optimal PAE degradation in soil was at pH 7 and 30
°C. The degradation of PAE was enhanced when DBP and DEHP were simultaneously present in the soil. The addition of either of the two types of compost individually also improved the rate of PAE degradation. Compost samples were separated into fractions with various particle size ranges, which spanned from 0.1–0.45 to 500–2000
μm. We observed that the compost fractions with smaller particle sizes demonstrated higher PAE degradation rates. When the different compost fractions were added to soil, however, compost particle size had no significant effect on the rate of PAE degradation.
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