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1.
Science of The Total Environment ; 863:160769, 2023.
Article in English | ScienceDirect | ID: covidwho-2159792

ABSTRACT

Carbonyls have attracted continuous attention due to their critical roles in atmospheric chemistry and their potential hazards to the ecological environment and human health. In this study, atmospheric carbonyls were measured during several ground-level-ozone (O3) pollution episodes at three urban sites (CRAES, IEP and BJUT) in Beijing in 2019 and 2020. Comparative analysis revealed that the carbonyl concentrations were 20.25 ± 6.91 ppb and 13.43 ± 5.13 ppb in 2019 and 2020 in Beijing, respectively, with a significant spatial trend from north to south, and carbonyl levels in urban Beijing were in an upper-intermediate range in China, and higher than those in other countries reported in the literature. A particularly noteworthy phenomenon is the consistency of carbonyl concentrations with variations in O3 concentrations. On O3 polluted days, the carbonyl concentrations were 1.3–1.5 times higher than those on non-O3 polluted days. Secondary formation contributed more to formaldehyde (FA) and acetaldehyde (AA) on O3 polluted days, while the anthropogenic emissions were more significant for acetone (AC) on non-O3 polluted days. Vehicle exhaust and solvent utilization were the main primary contributors to carbonyls. Due to reduced anthropogenic emissions caused by the COVID-19 lockdown and the "Program for Controlling Volatile Organic Compounds in 2020” in China, the contributions of primary emissions to carbonyls decreased in 2020 in Beijing. Human cancer risks to exposed populations from FA and AA increased with elevated O3 levels, and the risks still remained on non-O3 polluted days. The residents around the BJUT site might experience relatively higher human cancer risks than those around the other two sites. The findings in this study confirmed that atmospheric carbonyl pollution and its potential human health hazards cannot be ignored in urban Beijing;therefore, more strict control strategies for atmospheric carbonyls are urgently needed to better protect human health in Beijing in the future.

2.
Frontiers in cellular and infection microbiology ; 12, 2022.
Article in English | EuropePMC | ID: covidwho-1989772

ABSTRACT

The gut microbiome profile of COVID-19 patients was found to correlate with a viral load of SARS-CoV-2, COVID-19 severity, and dysfunctional immune responses, suggesting that gut microbiota may be involved in anti-infection. In order to investigate the role of gut microbiota in anti-infection against SARS-CoV-2, we established a high-throughput in vitro screening system for COVID-19 therapeutics by targeting the endoribonuclease (Nsp15). We also evaluated the activity inhibition of the target by substances of intestinal origin, using a mouse model in an attempt to explore the interactions between gut microbiota and SARS-CoV-2. The results unexpectedly revealed that antibiotic treatment induced the appearance of substances with Nsp15 activity inhibition in the intestine of mice. Comprehensive analysis based on functional profiling of the fecal metagenomes and endoribonuclease assay of antibiotic-enriched bacteria and metabolites demonstrated that the Nsp15 inhibitors were the primary bile acids that accumulated in the gut as a result of antibiotic-induced deficiency of bile acid metabolizing microbes. This study provides a new perspective on the development of COVID-19 therapeutics using primary bile acids.

3.
Signal Transduct Target Ther ; 6(1): 110, 2021 03 06.
Article in English | MEDLINE | ID: covidwho-1118799

ABSTRACT

The 2019 coronavirus disease (COVID-19) outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency. However, the virus' pathogenesis remains unclear, and there is no cure for the disease. We investigated the dynamic changes of blood immune response in patients with COVID-19 at different stages by using 5' gene expression, T cell receptor (TCR), and B cell receptors (BCR) V(D)J transcriptome analysis at a single-cell resolution. We obtained single-cell mRNA sequencing (scRNA-seq) data of 341,420 peripheral blood mononuclear cells (PBMCs) and 185,430 clonotypic T cells and 28,802 clonotypic B cells from 25 samples of 16 patients with COVID-19 for dynamic studies. In addition, we used three control samples. We found expansion of dendritic cells (DCs), CD14+ monocytes, and megakaryocytes progenitor cells (MP)/platelets and a reduction of naïve CD4+ T lymphocytes in patients with COVID-19, along with a significant decrease of CD8+ T lymphocytes, and natural killer cells (NKs) in patients in critical condition. The type I interferon (IFN-I), mitogen-activated protein kinase (MAPK), and ferroptosis pathways were activated while the disease was active, and recovered gradually after patient conditions improved. Consistent with this finding, the mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls. The concentration of interferon-α (IFN-α) in the serum of patients with COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with COVID-19 and 106 controls, further suggesting the important role of the IFN-I pathway in the immune response of COVID-19. TCR and BCR sequences analyses indicated that patients with COVID-19 developed specific immune responses against SARS-CoV-2 antigens. Our study reveals a dynamic landscape of human blood immune responses to SARS-CoV-2 infection, providing clues for therapeutic potentials in treating COVID-19.


Subject(s)
COVID-19/immunology , Leukocytes/immunology , Receptors, Antigen, B-Cell/immunology , Receptors, Antigen, T-Cell/immunology , SARS-CoV-2/immunology , Single-Cell Analysis , Adult , COVID-19/genetics , Female , Ferroptosis/genetics , Ferroptosis/immunology , Humans , MAP Kinase Signaling System/genetics , MAP Kinase Signaling System/immunology , Male , Middle Aged , RNA-Seq , Receptors, Antigen, B-Cell/genetics , Receptors, Antigen, T-Cell/genetics , SARS-CoV-2/genetics
4.
Nat Commun ; 12(1): 1346, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1111984

ABSTRACT

SARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-level of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/pathogenicity , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Blotting, Western , COVID-19/therapy , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunity, Cellular/physiology , Immunization, Passive , Immunohistochemistry , Macaca mulatta , Mice , Mice, Inbred BALB C , Microscopy, Electron , SARS-CoV-2/immunology
5.
J Raman Spectrosc ; 52(5): 949-958, 2021 May.
Article in English | MEDLINE | ID: covidwho-1095641

ABSTRACT

The outbreak of COVID-19 coronavirus disease around the end of 2019 has become a pandemic. The preferred method for COVID-19 detection is the real-time polymerase chain reaction (RT-PCR)-based technique; however, it also has certain limitations, such as sample-dependent procedures with a relatively high false negative ratio. We propose a safe and efficient method for screening COVID-19 based on Raman spectroscopy. A total of 177 serum samples are collected from 63 confirmed COVID-19 patients, 59 suspected cases, and 55 healthy individuals as a control group. Raman spectroscopy is adopted to analyze these samples, and a machine learning support-vector machine (SVM) method is applied to the spectrum dataset to build a diagnostic algorithm. Furthermore, 20 independent individuals, including 5 asymptomatic COVID-19 patients and 5 symptomatic COVID-19 patients, 5 suspected patients, and 5 healthy patients, were sampled for external validation. In these three groups-confirmed COVID-19, suspected, and healthy individuals-the distribution of statistically significant points of difference showed highly consistency for intergroups after repeated sampling processes. The classification accuracy between the COVID-19 cases and the suspected cases is 0.87 (95% confidence interval [CI]: 0.85-0.88), and the accuracy between the COVID-19 and the healthy controls is 0.90 (95% CI: 0.89-0.91), while the accuracy between the suspected cases and the healthy control group is 0.68 (95% CI: 0.67-0.73). For the independent test dataset, we apply the obtained SVM model to the classification of the independent test dataset to have all the results correctly classified. Our model showed that the serum-level classification results were all correct for independent test dataset. Our results suggest that Raman spectroscopy could be a safe and efficient technique for COVID-19 screening.

6.
Transfusion ; 60(12): 2952-2961, 2020 12.
Article in English | MEDLINE | ID: covidwho-717336

ABSTRACT

BACKGROUND: The ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused great global concerns. In contrast to SARS, some SARS-CoV-2-infected people can be asymptomatic or have only mild nonspecific symptoms. Furthermore, there is evidence that SARS-CoV-2 may be infectious during an asymptomatic incubation period. With the discovery that SARS-CoV-2 can be detected in plasma or serum, blood safety is worthy of consideration. STUDY DESIGN AND METHODS: We developed a nucleic acid test (NAT) screening system for SARS-CoV-2 targeting nucleocapsid protein (N) and open reading frame 1ab (ORF 1ab) gene that could screen 5076 samples every 24 hours. The 2019 novel coronavirus RNA standard was used to evaluate linearity of standard curves. Diagnostic sensitivity and reproducibility were evaluated using artificial SARS-CoV-2. Specificity was evaluated with 61 other respiratory pathogens. Diagnostic performance was evaluated by testing two sputum and nine oropharyngeal swab specimens. The reverse transcription polymerase chain reaction (RT-PCR) assay was used to screen SARS-CoV-2 RNA in blood donor specimens collected during the outbreak of SARS-CoV-2 in Chengdu. RESULTS: Limits of detection of the SARS-CoV-2 RT-PCR assay for N and ORF 1ab gene were 12.5 and 27.58 copies/mL, respectively. Intra-assay and interassay for the SARS-CoV-2 RT-PCR assay based on cycle threshold were acceptably low. No cross-reactivity was observed with other respiratory virus and bacterial isolates. The overall agreement value between the SARS-CoV-2 RT-PCR assay and clinical diagnostic results was 100%. A total of 16 287 blood specimens collected from blood donors during SARS-CoV-2 surveillance were tested negative. CONCLUSIONS: A high-throughput NAT screening system was developed for SARS-CoV-2 screening of blood donations during the outbreak of SARS-CoV-2.


Subject(s)
Blood Donors , COVID-19 Nucleic Acid Testing/methods , COVID-19/blood , Donor Selection/methods , High-Throughput Screening Assays/methods , Pandemics , RNA, Viral/blood , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2/isolation & purification , Artifacts , COVID-19/virology , DNA Primers , Hemoglobins/analysis , Humans , Lipids/blood , Oropharynx/virology , RNA, Viral/isolation & purification , Reproducibility of Results , Sensitivity and Specificity , Sputum/virology
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