cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.19317936
title: Adverse events of special interest following the use of BNT162b2 in adolescents: a population-based retrospective cohort study

description: Accruing evidence suggests an increased risk of myocarditis in adolescents from messenger RNA COVID-19 vaccines. However, other potential adverse events remain under-researched. We conducted a retrospective cohort study of adolescents aged 12–18 with a territory-wide electronic healthcare database of the Hong Kong population linked with population-based vaccination records and supplemented with age- and sex-specific population numbers. Two age- and sex-matched retrospective cohorts were formed to observe 28 days following the first and second doses of BNT162b2 and estimate the age- and sex-adjusted incidence rate ratios between the vaccinated and unvaccinated. Thirty AESIs adapted from the World Health Organization’s Global Advisory Committee on Vaccine Safety were examined. Eventually, the first-dose cohort comprised 274,881 adolescents (50.25% received the first dose) and the second-dose cohort 237,964 (50.29% received the second dose). Ninety-four (34.2 per 100,000 persons) adolescents in the first-dose cohort and 130 (54.6 per 100,000 persons) in the second-dose cohort experienced ≥1 AESIs. There were no statistically significant differences in the risk of any AESI associated with BNT162b2 except myocarditis [first-dose cohort: incidence rate ratio (IRR) = 9.15, 95% confidence interval (CI) 1.14–73.16; second-dose cohort: IRR = 29.61, 95% CI 4.04–217.07] and sleeping disturbances/disorders after the second dose (IRR = 2.06, 95% CI 1.01–4.24). Sensitivity analysis showed that, with myocarditis excluded as AESIs, no significantly elevated risk of AESIs as a composite outcome associated with vaccination was observed (<i>P </i>= 0.195). To conclude, the overall absolute risk of AESIs was low with no evidence of an increased risk of AESIs except myocarditis and sleeping disturbances/disorders.
DOI: 10.6084/m9.figshare.19317936.v2
title: Adverse events of special interest following the use of BNT162b2 in adolescents: a population-based retrospective cohort study

description: Accruing evidence suggests an increased risk of myocarditis in adolescents from messenger RNA COVID-19 vaccines. However, other potential adverse events remain under-researched. We conducted a retrospective cohort study of adolescents aged 12–18 with a territory-wide electronic healthcare database of the Hong Kong population linked with population-based vaccination records and supplemented with age- and sex-specific population numbers. Two age- and sex-matched retrospective cohorts were formed to observe 28 days following the first and second doses of BNT162b2 and estimate the age- and sex-adjusted incidence rate ratios between the vaccinated and unvaccinated. Thirty AESIs adapted from the World Health Organization’s Global Advisory Committee on Vaccine Safety were examined. Eventually, the first-dose cohort comprised 274,881 adolescents (50.25% received the first dose) and the second-dose cohort 237,964 (50.29% received the second dose). Ninety-four (34.2 per 100,000 persons) adolescents in the first-dose cohort and 130 (54.6 per 100,000 persons) in the second-dose cohort experienced ≥1 AESIs. There were no statistically significant differences in the risk of any AESI associated with BNT162b2 except myocarditis [first-dose cohort: incidence rate ratio (IRR) = 9.15, 95% confidence interval (CI) 1.14–73.16; second-dose cohort: IRR = 29.61, 95% CI 4.04–217.07] and sleeping disturbances/disorders after the second dose (IRR = 2.06, 95% CI 1.01–4.24). Sensitivity analysis showed that, with myocarditis excluded as AESIs, no significantly elevated risk of AESIs as a composite outcome associated with vaccination was observed (<i>P </i>= 0.195). To conclude, the overall absolute risk of AESIs was low with no evidence of an increased risk of AESIs except myocarditis and sleeping disturbances/disorders.
DOI: 10.6084/m9.figshare.19431362
title: SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in an Arf6-dependent manner

description: The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants is threatening public health around the world. Endocytosis functions as an important way for viral infection, and SARS-CoV-2 bears no exception. However, the specific endocytic mechanism of SARS-CoV-2 remains unknown. In this study, we used endocytic inhibitors to evaluate the role of different endocytic routes in SARS-CoV-2 pseudovirus infection and found that the viral infection was associated with caveolar/lipid raft- and cytoskeleton-mediated endocytosis, but independent of the clathrin-mediated endocytosis and macropinocytosis. Meanwhile, the knockdown of CD147 and Rab5a in Vero E6 and Huh-7 cells inhibited SARS-CoV-2 pseudovirus infection, and the co-localization of spike protein, CD147, and Rab5a was observed in pseudovirus-infected Vero E6 cells, which was weakened by CD147 silencing, illustrating that SARS-CoV-2 pseudovirus entered the host cells via CD147-mediated endocytosis. Additionally, Arf6 silencing markedly inhibited pseudovirus infection in Vero E6 and Huh-7 cells, while little change was observed in CD147 knockout-Vero E6 cells. This finding indicated Arf6-mediated CD147 trafficking plays a vital role in SARS-CoV-2 entry. Taken together, our findings provide new insights into the CD147-Arf6 axis in mediating SARS-CoV-2 pseudovirus entry into the host cells, and further suggest that blockade of this pathway seems to be a feasible approach to prevent the SARS-CoV-2 infection clinically.
DOI: 10.6084/m9.figshare.19431362.v2
title: SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in an Arf6-dependent manner

description: The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants is threatening public health around the world. Endocytosis functions as an important way for viral infection, and SARS-CoV-2 bears no exception. However, the specific endocytic mechanism of SARS-CoV-2 remains unknown. In this study, we used endocytic inhibitors to evaluate the role of different endocytic routes in SARS-CoV-2 pseudovirus infection and found that the viral infection was associated with caveolar/lipid raft- and cytoskeleton-mediated endocytosis, but independent of the clathrin-mediated endocytosis and macropinocytosis. Meanwhile, the knockdown of CD147 and Rab5a in Vero E6 and Huh-7 cells inhibited SARS-CoV-2 pseudovirus infection, and the co-localization of spike protein, CD147, and Rab5a was observed in pseudovirus-infected Vero E6 cells, which was weakened by CD147 silencing, illustrating that SARS-CoV-2 pseudovirus entered the host cells via CD147-mediated endocytosis. Additionally, Arf6 silencing markedly inhibited pseudovirus infection in Vero E6 and Huh-7 cells, while little change was observed in CD147 knockout-Vero E6 cells. This finding indicated Arf6-mediated CD147 trafficking plays a vital role in SARS-CoV-2 entry. Taken together, our findings provide new insights into the CD147-Arf6 axis in mediating SARS-CoV-2 pseudovirus entry into the host cells, and further suggest that blockade of this pathway seems to be a feasible approach to prevent the SARS-CoV-2 infection clinically.
DOI: 10.6084/m9.figshare.30546217
title: Analysis of SARS-CoV-2 variants B.1.617: host tropism, proteolytic activation, cell–cell fusion, and neutralization sensitivity

description: SARS-CoV-2 has caused the COVID-19 pandemic. B.1.617 variants (including Kappa and Delta) have been transmitted rapidly in India. The transmissibility, pathogenicity, and neutralization characteristics of these variants have received considerable interest. In this study, 22 pseudotyped viruses were constructed for B.1.617 variants and their corresponding single amino acid mutations. B.1.617 variants did not exhibit significant enhanced infectivity in human cells, but mutations T478K and E484Q in the receptor binding domain led to enhanced infectivity in mouse ACE2-overexpressing cells. Furin activities were slightly increased against B.1.617 variants and cell–cell fusion after infection of B.1.617 variants were enhanced. Furthermore, B.1.617 variants escaped neutralization by several mAbs, mainly because of mutations L452R, T478K, and E484Q in the receptor binding domain. The neutralization activities of sera from convalescent patients, inactivated vaccine-immunized volunteers, adenovirus vaccine-immunized volunteers, and SARS-CoV-2 immunized animals against pseudotyped B.1.617 variants were reduced by approximately twofold, compared with the D614G variant.
DOI: 10.6084/m9.figshare.30546217.v1
title: Analysis of SARS-CoV-2 variants B.1.617: host tropism, proteolytic activation, cell–cell fusion, and neutralization sensitivity

description: SARS-CoV-2 has caused the COVID-19 pandemic. B.1.617 variants (including Kappa and Delta) have been transmitted rapidly in India. The transmissibility, pathogenicity, and neutralization characteristics of these variants have received considerable interest. In this study, 22 pseudotyped viruses were constructed for B.1.617 variants and their corresponding single amino acid mutations. B.1.617 variants did not exhibit significant enhanced infectivity in human cells, but mutations T478K and E484Q in the receptor binding domain led to enhanced infectivity in mouse ACE2-overexpressing cells. Furin activities were slightly increased against B.1.617 variants and cell–cell fusion after infection of B.1.617 variants were enhanced. Furthermore, B.1.617 variants escaped neutralization by several mAbs, mainly because of mutations L452R, T478K, and E484Q in the receptor binding domain. The neutralization activities of sera from convalescent patients, inactivated vaccine-immunized volunteers, adenovirus vaccine-immunized volunteers, and SARS-CoV-2 immunized animals against pseudotyped B.1.617 variants were reduced by approximately twofold, compared with the D614G variant.
DOI: 10.6084/m9.figshare.19613914
title: MCR-1-dependent lipid remodelling compromises the viability of Gram-negative bacteria

description: The global dissemination of the mobilized colistin resistance gene, <i>mcr-1</i>, threatens human health. Recent studies by our group and others have shown that the withdrawal of colistin as a feed additive dramatically reduced the prevalence of <i>mcr-1</i>. Although it is accepted that the rapid reduction in <i>mcr-1</i> prevalence may have resulted, to some extent, from the toxic effects of MCR-1, the detailed mechanism remains unclear. Here, we found that MCR-1 damaged the outer membrane (OM) permeability in <i>Escherichia coli</i> and <i>Klebsiella pneumonia</i> and that this event was associated with MCR-1-mediated cell shrinkage and death during the stationary phase. Notably, the capacity of MCR-1-expressing cells for recovery from the stationary phase under improved conditions was reduced in a time-dependent manner. We also showed that mutations in the potential lipid-A-binding pocket of MCR-1, but not in the catalytic domain, restored OM permeability and cell viability. During the stationary phase, PbgA, a sensor of periplasmic lipid-A and LpxC production that performed the first step in lipid-A synthesis, was reduced after MCR-1 expression, suggesting that MCR-1 disrupted lipid homeostasis. Consistent with this, the overexpression of LpxC completely reversed the MCR-1-induced OM permeability defect. We propose that MCR-1 causes lipid remodelling that results in an OM permeability defect, thus compromising the viability of Gram-negative bacteria. These findings extended our understanding of the effect of MCR-1 on bacterial physiology and provided a potential strategy for eliminating drug-resistant bacteria.
DOI: 10.6084/m9.figshare.19613914.v5
title: MCR-1-dependent lipid remodelling compromises the viability of Gram-negative bacteria

description: The global dissemination of the mobilized colistin resistance gene, <i>mcr-1</i>, threatens human health. Recent studies by our group and others have shown that the withdrawal of colistin as a feed additive dramatically reduced the prevalence of <i>mcr-1</i>. Although it is accepted that the rapid reduction in <i>mcr-1</i> prevalence may have resulted, to some extent, from the toxic effects of MCR-1, the detailed mechanism remains unclear. Here, we found that MCR-1 damaged the outer membrane (OM) permeability in <i>Escherichia coli</i> and <i>Klebsiella pneumonia</i> and that this event was associated with MCR-1-mediated cell shrinkage and death during the stationary phase. Notably, the capacity of MCR-1-expressing cells for recovery from the stationary phase under improved conditions was reduced in a time-dependent manner. We also showed that mutations in the potential lipid-A-binding pocket of MCR-1, but not in the catalytic domain, restored OM permeability and cell viability. During the stationary phase, PbgA, a sensor of periplasmic lipid-A and LpxC production that performed the first step in lipid-A synthesis, was reduced after MCR-1 expression, suggesting that MCR-1 disrupted lipid homeostasis. Consistent with this, the overexpression of LpxC completely reversed the MCR-1-induced OM permeability defect. We propose that MCR-1 causes lipid remodelling that results in an OM permeability defect, thus compromising the viability of Gram-negative bacteria. These findings extended our understanding of the effect of MCR-1 on bacterial physiology and provided a potential strategy for eliminating drug-resistant bacteria.
DOI: 10.6084/m9.figshare.19709887
title: Virulence adaption to environment promotes the age-dependent nasal colonization of <i>Staphylococcus aureus</i>

description: <i>Staphylococcus aureus</i> is an important human commensal bacteria colonizing the human body, especially the nasal cavity. The nasal carriage can be a source of <i>S. aureus</i> bacteremia. However, the bacterial factors contributing to nasal colonization are not completely understood. By analysing <i>S. aureus</i> strains from the nasal cavity of the children, young adults, and seniors, we found that the low activity of the SaeRS two-component system (TCS) is an important determinant for <i>S. aureus</i> to colonize in seniors. The senior group isolates of <i>S. aureus</i> showed a rather distinct sequence type composition as compared with other age group isolates. The senior group isolates showed not only a lower gene carriage of enterotoxins a, c, and q but also lower hemolytic activity against human red blood cells. Of regulators affecting hemolysin production (i.e. <i>agr</i>, <i>saeRS</i>, <i>rot</i>, <i>rsp</i>, and <i>sarS</i>), only the SaeRS TCS showed an age-dependent decrease of activity. The decreased virulence and better colonization ability of the senior group isolates of <i>S. aureus</i> were confirmed in the mouse model. The senior group isolates showed the lowest survival and the best adhesion and colonizing ability. Also, the senior nasal secretions supported <i>S. aureus</i> survival better than the child and young adult nasal secretions. These results indicated that the senior nasal cavity favours colonization of <i>S. aureus</i> with higher adhesion and lower virulence, to which the reduced SaeRS TCS activity contributes. Taken together, our results illustrate an example of bacterial adaptation to the changing host environment.
DOI: 10.6084/m9.figshare.19709887.v2
title: Virulence adaption to environment promotes the age-dependent nasal colonization of <i>Staphylococcus aureus</i>

description: <i>Staphylococcus aureus</i> is an important human commensal bacteria colonizing the human body, especially the nasal cavity. The nasal carriage can be a source of <i>S. aureus</i> bacteremia. However, the bacterial factors contributing to nasal colonization are not completely understood. By analysing <i>S. aureus</i> strains from the nasal cavity of the children, young adults, and seniors, we found that the low activity of the SaeRS two-component system (TCS) is an important determinant for <i>S. aureus</i> to colonize in seniors. The senior group isolates of <i>S. aureus</i> showed a rather distinct sequence type composition as compared with other age group isolates. The senior group isolates showed not only a lower gene carriage of enterotoxins a, c, and q but also lower hemolytic activity against human red blood cells. Of regulators affecting hemolysin production (i.e. <i>agr</i>, <i>saeRS</i>, <i>rot</i>, <i>rsp</i>, and <i>sarS</i>), only the SaeRS TCS showed an age-dependent decrease of activity. The decreased virulence and better colonization ability of the senior group isolates of <i>S. aureus</i> were confirmed in the mouse model. The senior group isolates showed the lowest survival and the best adhesion and colonizing ability. Also, the senior nasal secretions supported <i>S. aureus</i> survival better than the child and young adult nasal secretions. These results indicated that the senior nasal cavity favours colonization of <i>S. aureus</i> with higher adhesion and lower virulence, to which the reduced SaeRS TCS activity contributes. Taken together, our results illustrate an example of bacterial adaptation to the changing host environment.
DOI: 10.6084/m9.figshare.19613914.v4
title: MCR-1-dependent lipid remodelling compromises the viability of Gram-negative bacteria

description: The global dissemination of the mobilized colistin resistance gene, <i>mcr-1</i>, threatens human health. Recent studies by our group and others have shown that the withdrawal of colistin as a feed additive dramatically reduced the prevalence of <i>mcr-1</i>. Although it is accepted that the rapid reduction in <i>mcr-1</i> prevalence may have resulted, to some extent, from the toxic effects of MCR-1, the detailed mechanism remains unclear. Here, we found that MCR-1 damaged the outer membrane (OM) permeability in <i>Escherichia coli</i> and <i>Klebsiella pneumonia</i> and that this event was associated with MCR-1-mediated cell shrinkage and death during the stationary phase. Notably, the capacity of MCR-1-expressing cells for recovery from the stationary phase under improved conditions was reduced in a time-dependent manner. We also showed that mutations in the potential lipid-A-binding pocket of MCR-1, but not in the catalytic domain, restored OM permeability and cell viability. During the stationary phase, PbgA, a sensor of periplasmic lipid-A and LpxC production that performed the first step in lipid-A synthesis, was reduced after MCR-1 expression, suggesting that MCR-1 disrupted lipid homeostasis. Consistent with this, the overexpression of LpxC completely reversed the MCR-1-induced OM permeability defect. We propose that MCR-1 causes lipid remodelling that results in an OM permeability defect, thus compromising the viability of Gram-negative bacteria. These findings extended our understanding of the effect of MCR-1 on bacterial physiology and provided a potential strategy for eliminating drug-resistant bacteria.
DOI: 10.6084/m9.figshare.20110305
title: Modulation of viral replication, apoptosis and antiviral response by induction and mutual regulation of EGR and AP-1 family genes during coronavirus infection

description: Coronaviruses have evolved a variety of strategies to exploit normal cellular processes and signalling pathways for their efficient reproduction in a generally hostile cellular environment. One immediate-early response gene (IEG) family, the AP-1 gene family, was previously shown to be activated by coronavirus infection. In this study, we report that another IEG family, the EGR family, is also activated in cells infected with four different coronaviruses in three genera, i.e. gammacoronavirus infectious bronchitis virus (IBV), alphacoronaviruses porcine epidemic diarrhoea virus (PEDV) and human coronavirus-229E (HCoV-229E), and betacoronavirus HCoV-OC43. Knockdown of EGR1 reduced the expression of cJUN and cFOS, and knockdown of cJUN and/or cFOS reduced the expression of EGR1, demonstrating that these two IEG families may be cross-activated and mutual regulated. Furthermore, ERK1/2 was identified as an upstream kinase, and JNK and p38 as inhibitors of EGR1 activation in coronavirus-infected cells. However, upregulation of EGR family genes, in particular EGR1, appears to play a differential role in regulating viral replication, apoptosis and antiviral response. EGR1 was shown to play a limited role in regulation of coronavirus replication, and an anti-apoptotic role in cells infected with IBV or PEDV, but not in cells infected with HCoV-229E. Upregulation of EGR1 may also play a differential role in the regulation of antiviral response against different coronaviruses. This study reveals a novel regulatory network shared by different coronaviruses in the immediate-early response of host cells to infection.
DOI: 10.6084/m9.figshare.20110305.v2
title: Modulation of viral replication, apoptosis and antiviral response by induction and mutual regulation of EGR and AP-1 family genes during coronavirus infection

description: Coronaviruses have evolved a variety of strategies to exploit normal cellular processes and signalling pathways for their efficient reproduction in a generally hostile cellular environment. One immediate-early response gene (IEG) family, the AP-1 gene family, was previously shown to be activated by coronavirus infection. In this study, we report that another IEG family, the EGR family, is also activated in cells infected with four different coronaviruses in three genera, i.e. gammacoronavirus infectious bronchitis virus (IBV), alphacoronaviruses porcine epidemic diarrhoea virus (PEDV) and human coronavirus-229E (HCoV-229E), and betacoronavirus HCoV-OC43. Knockdown of EGR1 reduced the expression of cJUN and cFOS, and knockdown of cJUN and/or cFOS reduced the expression of EGR1, demonstrating that these two IEG families may be cross-activated and mutual regulated. Furthermore, ERK1/2 was identified as an upstream kinase, and JNK and p38 as inhibitors of EGR1 activation in coronavirus-infected cells. However, upregulation of EGR family genes, in particular EGR1, appears to play a differential role in regulating viral replication, apoptosis and antiviral response. EGR1 was shown to play a limited role in regulation of coronavirus replication, and an anti-apoptotic role in cells infected with IBV or PEDV, but not in cells infected with HCoV-229E. Upregulation of EGR1 may also play a differential role in the regulation of antiviral response against different coronaviruses. This study reveals a novel regulatory network shared by different coronaviruses in the immediate-early response of host cells to infection.