cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.28914993
title: Serum metabolomic characteristics of COVID-19 patients co-infection with echovirus

description: Currently, the Omicron variant of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to circulate globally. In our multiplex respiratory pathogen detection, we identified numerous instances of co-infection with Echovirus (ECHO) among Coronavirus Disease 2019 (COVID-19) patients, which exacerbated the clinical symptoms of these patients. Such co-infections are likely to impact the subsequent medical treatment. To date, there are no reports on the pathogenic mechanisms related to COVID-19 co-infected with ECHO. Therefore, this study employed the TM Widely-Targeted metabolomics approach to analyze the serum metabolomes of COVID-19 patients with single SARS-CoV-2 infection (COVID-19), COVID-19 patients co-infected with ECHO (COVID-19  +  ECHO), and healthy individuals (Control) recruited from routine physical examinations during the same period. Concurrent clinical laboratory tests were performed on the patients to reveal the differences in metabolomic characteristics between the COVID-19 patients and the COVID-19  +  ECHO patients, as well as to explore potential metabolic pathways that may exacerbate disease progression. Our findings indicate that both clinical examination indicators and the pathways enriched by differential metabolites confirm that patients with dual infection exhibit higher inflammatory and immune responses compared to those with single COVID-19 infections. This difference is likely reflected through abnormalities in the glycerophospholipid metabolic pathway, with the metabolite Sn-Glycero-3-Phosphocholine playing a crucial role in this process. Finally, we established a diagnostic model based on logistic regression using five differential metabolites, which accurately differentiates between the dual infection population and the single COVID-19 infection population (AUC = 0.828).
DOI: 10.6084/m9.figshare.28914993.v1
title: Serum metabolomic characteristics of COVID-19 patients co-infection with echovirus

description: Currently, the Omicron variant of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to circulate globally. In our multiplex respiratory pathogen detection, we identified numerous instances of co-infection with Echovirus (ECHO) among Coronavirus Disease 2019 (COVID-19) patients, which exacerbated the clinical symptoms of these patients. Such co-infections are likely to impact the subsequent medical treatment. To date, there are no reports on the pathogenic mechanisms related to COVID-19 co-infected with ECHO. Therefore, this study employed the TM Widely-Targeted metabolomics approach to analyze the serum metabolomes of COVID-19 patients with single SARS-CoV-2 infection (COVID-19), COVID-19 patients co-infected with ECHO (COVID-19  +  ECHO), and healthy individuals (Control) recruited from routine physical examinations during the same period. Concurrent clinical laboratory tests were performed on the patients to reveal the differences in metabolomic characteristics between the COVID-19 patients and the COVID-19  +  ECHO patients, as well as to explore potential metabolic pathways that may exacerbate disease progression. Our findings indicate that both clinical examination indicators and the pathways enriched by differential metabolites confirm that patients with dual infection exhibit higher inflammatory and immune responses compared to those with single COVID-19 infections. This difference is likely reflected through abnormalities in the glycerophospholipid metabolic pathway, with the metabolite Sn-Glycero-3-Phosphocholine playing a crucial role in this process. Finally, we established a diagnostic model based on logistic regression using five differential metabolites, which accurately differentiates between the dual infection population and the single COVID-19 infection population (AUC = 0.828).
DOI: 10.6084/m9.figshare.29572690
title: A systematic survey of type I secretion systems and their substrate proteins in <i>Salmonella</i>

description: Type I secretion systems (T1SSs) and the substrates have not been investigated extensively in <i>Salmonella</i>, despite their potential significance. In this research, we screened the comprehensive list of <i>Salmonella</i> T1SSs, observed their evolution and transcriptional regulation, predicted the substrates and explored their sequence and structural properties. In total, 61 sets of T1SSs were captured from the genomes of 26 representative strains covering the known <i>Salmonella</i> species and subspecies. The T1SSs fall into 4 clusters. Clusters I and II are conserved and were potentially acquired anciently before the diversification of the <i>Salmonella</i> genus, Cluster III was also anciently acquired but lost in many <i>S. enterica</i> subspecies and strains, and Cluster IV is unconserved and could have been acquired by individual strains through horizontal transferring events. The Cluster II T1SS gene cluster is transcriptionally co-regulated with the operons of <i>Salmonella</i> Pathogenic Island 1 (SPI-1) type III secretion system (T3SS) gene cluster, the effector genes, and other virulence genes, while HilC could potentially be a key regulator for the network. We also predicted 159 potential T1SS substrates from the strains. The putative SiiE-family Cluster II T1SS substrates showed apparent sequence diversity, attributed to recombination, gene fission, fragmental deletion, and point mutation. However, the variants of SiiE proteins appeared structurally conserved and secretable through T1SS conduits, including the two shorter peptides derived from the split <i>siiE</i> genes in <i>S</i>. Typhi strains. Taken together, the study broadened our knowledge about the T1SSs in <i>Salmonella</i>, their evolution and the SiiE-mediated bacterial pathogenicity.
DOI: 10.6084/m9.figshare.29572690.v1
title: A systematic survey of type I secretion systems and their substrate proteins in <i>Salmonella</i>

description: Type I secretion systems (T1SSs) and the substrates have not been investigated extensively in <i>Salmonella</i>, despite their potential significance. In this research, we screened the comprehensive list of <i>Salmonella</i> T1SSs, observed their evolution and transcriptional regulation, predicted the substrates and explored their sequence and structural properties. In total, 61 sets of T1SSs were captured from the genomes of 26 representative strains covering the known <i>Salmonella</i> species and subspecies. The T1SSs fall into 4 clusters. Clusters I and II are conserved and were potentially acquired anciently before the diversification of the <i>Salmonella</i> genus, Cluster III was also anciently acquired but lost in many <i>S. enterica</i> subspecies and strains, and Cluster IV is unconserved and could have been acquired by individual strains through horizontal transferring events. The Cluster II T1SS gene cluster is transcriptionally co-regulated with the operons of <i>Salmonella</i> Pathogenic Island 1 (SPI-1) type III secretion system (T3SS) gene cluster, the effector genes, and other virulence genes, while HilC could potentially be a key regulator for the network. We also predicted 159 potential T1SS substrates from the strains. The putative SiiE-family Cluster II T1SS substrates showed apparent sequence diversity, attributed to recombination, gene fission, fragmental deletion, and point mutation. However, the variants of SiiE proteins appeared structurally conserved and secretable through T1SS conduits, including the two shorter peptides derived from the split <i>siiE</i> genes in <i>S</i>. Typhi strains. Taken together, the study broadened our knowledge about the T1SSs in <i>Salmonella</i>, their evolution and the SiiE-mediated bacterial pathogenicity.
DOI: 10.6084/m9.figshare.30762235
title: Genome-scale CRISPR screen identifies host factors associated with bovine parainfluenza virus 3 infection

description: Bovine parainfluenza virus type 3 (BPIV-3) is a major pathogen associated with the bovine respiratory disease complex. However, the limited understanding of host factors crucial for BPIV-3 replication has hindered the development of effective preventive and therapeutic strategies. To tackle this critical issue, we constructed a bovine genome-wide CRISPR/Cas9 knockout library in Madin-Darby bovine kidney cells, which was then used to systematically identify and characterize the host genes essential for BPIV-3a replication. Subsequently, 10 genes were validated using both RT-qPCR and viral titration assays. Furthermore, through gene knockout or knockdown and rescue experiments, we identified three key genes required for BPIV-3a replication: Wnt family member 5A (WNT5A), solute carrier family 16 member 13 (SLC16A13), and selenoprotein N (SELENON). However, their effects on viral adhesion and internalization varied. WNT5A was involved in both processes, SLC16A13 participated solely in internalization, while SELENON had no significant impact on either. Beyond BPIV-3a, these three genes were also found to be essential for the infection of BPIV-3c and Bovine enterovirus. In conclusion, this study offers novel insights into the molecular mechanisms governing the replication and pathogenesis of BPIV-3a, BPIV-3c, and bovine enterovirus within host cells, thereby providing a foundation for identifying potential targets in the development of novel antiviral strategies.
DOI: 10.6084/m9.figshare.30762235.v1
title: Genome-scale CRISPR screen identifies host factors associated with bovine parainfluenza virus 3 infection

description: Bovine parainfluenza virus type 3 (BPIV-3) is a major pathogen associated with the bovine respiratory disease complex. However, the limited understanding of host factors crucial for BPIV-3 replication has hindered the development of effective preventive and therapeutic strategies. To tackle this critical issue, we constructed a bovine genome-wide CRISPR/Cas9 knockout library in Madin-Darby bovine kidney cells, which was then used to systematically identify and characterize the host genes essential for BPIV-3a replication. Subsequently, 10 genes were validated using both RT-qPCR and viral titration assays. Furthermore, through gene knockout or knockdown and rescue experiments, we identified three key genes required for BPIV-3a replication: Wnt family member 5A (WNT5A), solute carrier family 16 member 13 (SLC16A13), and selenoprotein N (SELENON). However, their effects on viral adhesion and internalization varied. WNT5A was involved in both processes, SLC16A13 participated solely in internalization, while SELENON had no significant impact on either. Beyond BPIV-3a, these three genes were also found to be essential for the infection of BPIV-3c and Bovine enterovirus. In conclusion, this study offers novel insights into the molecular mechanisms governing the replication and pathogenesis of BPIV-3a, BPIV-3c, and bovine enterovirus within host cells, thereby providing a foundation for identifying potential targets in the development of novel antiviral strategies.
DOI: 10.6084/m9.figshare.29516669
title: Moderate altitude exposure impacts extensive host-microbiota multi-kingdom connectivity with serum metabolome and fasting blood glucose

description: The contributions and interactions of multi-kingdom microbiota (i.e. bacteriome, mycobiome, archaeome, and phageome) with serum metabolome and host phenome in healthy individuals under moderate altitude exposure remain unclear. We applied shotgun metagenomic sequencing in feces and targeted metabolomics technology in serum to explore how human gut multi-kingdom microorganisms influence the serum metabolome and phenome in healthy Chinese individuals following moderate altitude exposure. The results indicated that individuals with moderate altitude exposure exhibited more substantial alterations in gut bacteriome and phageome compared to those in mycobiome and archaeome. Both intra-kingdom and inter-kingdom correlations at baseline were denser than those following moderate altitude exposure. Bacteriophages-host interaction analysis revealed symbiosis between bacteriophages and <i>Bacteroidetes</i>, <i>Proteobacteria</i>, and short-chain fatty acids (SCFAs) producers. Furthermore, bacteriophage <i>Shirahamavirus PTm1</i> (odds ratio (OR) = 3.82; 95% confidence interval (CI): 1.20–12.16), archaeon <i>Crenarchaeota</i> (OR = 3.70; 95% CI: 1.35–10.14) and bacterium <i>Bacteroidetes</i> (OR = 3.69; 95% CI: 1.34–10.15) showed a positive association with lowered fasting blood glucose (FBG) benefits, while bacteriophage <i>Candidatus Nitrosopelagicus brevis</i> (OR = 0.30; 95% CI: 0.10–0.89) and butyric acid (OR = 0.07; 95% CI: 0.01–0.37) exhibited a negative association with lowered FBG benefits. These findings suggest that targeting gut multi-kingdom microorganisms could serve as an alternative therapeutic approach to mitigate dysglycemia and its associated metabolic disorders.
DOI: 10.6084/m9.figshare.29516669.v2
title: Moderate altitude exposure impacts extensive host-microbiota multi-kingdom connectivity with serum metabolome and fasting blood glucose

description: The contributions and interactions of multi-kingdom microbiota (i.e. bacteriome, mycobiome, archaeome, and phageome) with serum metabolome and host phenome in healthy individuals under moderate altitude exposure remain unclear. We applied shotgun metagenomic sequencing in feces and targeted metabolomics technology in serum to explore how human gut multi-kingdom microorganisms influence the serum metabolome and phenome in healthy Chinese individuals following moderate altitude exposure. The results indicated that individuals with moderate altitude exposure exhibited more substantial alterations in gut bacteriome and phageome compared to those in mycobiome and archaeome. Both intra-kingdom and inter-kingdom correlations at baseline were denser than those following moderate altitude exposure. Bacteriophages-host interaction analysis revealed symbiosis between bacteriophages and <i>Bacteroidetes</i>, <i>Proteobacteria</i>, and short-chain fatty acids (SCFAs) producers. Furthermore, bacteriophage <i>Shirahamavirus PTm1</i> (odds ratio (OR) = 3.82; 95% confidence interval (CI): 1.20–12.16), archaeon <i>Crenarchaeota</i> (OR = 3.70; 95% CI: 1.35–10.14) and bacterium <i>Bacteroidetes</i> (OR = 3.69; 95% CI: 1.34–10.15) showed a positive association with lowered fasting blood glucose (FBG) benefits, while bacteriophage <i>Candidatus Nitrosopelagicus brevis</i> (OR = 0.30; 95% CI: 0.10–0.89) and butyric acid (OR = 0.07; 95% CI: 0.01–0.37) exhibited a negative association with lowered FBG benefits. These findings suggest that targeting gut multi-kingdom microorganisms could serve as an alternative therapeutic approach to mitigate dysglycemia and its associated metabolic disorders.
DOI: 10.6084/m9.figshare.29516669.v1
title: Moderate altitude exposure impacts extensive host-microbiota multi-kingdom connectivity with serum metabolome and fasting blood glucose

description: The contributions and interactions of multi-kingdom microbiota (i.e. bacteriome, mycobiome, archaeaome, and phageome) with serum metabolome and host phenome in healthy individuals under moderate altitude exposure remain unclear. We applied shotgun metagenomic sequencing in faeces and targeted metabolomics technology in serum to explore how the human gut multi-kingdom microorganisms influence the serum metabolome and phenome in healthy Chinese individuals following moderate altitude exposure. The results indicated that individuals with moderate altitude exposure exhibited more substantial alterations in gut bacteriome and phageome compared to those in mycobiome and archaeaome. Both intra-kingdom and inter-kingdom correlations at baseline were denser than those following moderate altitude exposure. Bacteriophages-host interactions analysis revealed symbiosis between bacteriophages and <i>Bacteroidetes</i>, <i>Proteobacteria</i>, and short-chain fatty acids (SCFAs) producers. Furthermore, bacteriophage <i>Shirahamavirus PTm1</i> (odds ratio (OR) = 3.82; 95% confidence interval (CI): 1.20-12.16), archaeon <i>Crenarchaeota</i> (OR = 3.70; 95% CI: 1.35-10.14) and bacterium <i>Bacteroidetes</i> (OR = 3.69; 95% CI: 1.34-10.15) showed a positive association with lowered fasting blood glucose (FBG) benefits, while bacteriophage <i>Candidatus Nitrosopelagicus brevis</i> (OR = 0.30; 95% CI: 0.10-0.89) and butyric acid (OR = 0.07; 95% CI: 0.01-0.37) exhibited a negative association with lowered FBG benefits. These findings suggest that targeting gut multi-kingdom microorganisms could serve as an alternative therapeutic approach to mitigate dysglycemia and its associated metabolic disorders.
DOI: 10.6084/m9.figshare.30021796
title: Ubiquitin degradation of the Ribonuclease H2 subunit B Rnh2B regulates the virulence of <i>Cryptococcus neoformans</i>

description: The ubiquitin-proteasome system (UPS) regulates protein degradation in eukaryotes by polyubiquitinating substrate proteins, with F-box proteins serving as key components for substrate recognition. Research has shown that the absence of Cdc4, an F-box protein in <i>C. neoformans</i>, decreases virulence, yet the mechanisms by which Cdc4 affects these processes remain unclear. Using an iTRAQ-based proteomic strategy, we recognized Ribonuclease H2 subunit B (Rnh2B) as a target substrate for Cdc4. Protein-protein interaction assays have confirmed the interaction between Cdc4 and Rnh2B, indicating that Cdc4 regulates Rnh2B stability through ubiquitination. Functional analyses revealed that both the knockout and overexpression of <i>RNH2B</i> impair growth at 37°C, with the latter also affecting cellular membrane integrity and growth under osmotic stress conditions. Pathogenicity assays revealed that the deletion of <i>RNH2B</i> results in reduced virulence, whereas its overexpression leads to a complete loss of pathogenicity. Longitudinal tracking of fungal infection progression illustrated that mice lungs infected with <i>rnh2B</i>Δ mutants maintained a low yet stable fungal burden, in contrast to a significant reduction in fungal load observed in conjunction with <i>RNH2B</i> overexpression, ultimately leading to complete clearance. Analysis of host immune responses indicated a correlation between diminished virulence in the <i>RNH2B</i><sup>OE</sup> strain and robust host immune activation. Notably, both the <i>RNH2B</i><sup>OE</sup> strain and the <i>cdc4</i>Δ mutant induced analogous adaptive immune responses, facilitating the clearance of <i>C. neoformans</i> infection. Collectively, our findings propose a model wherein Cdc4 mediates the ubiquitination and degradation of Rnh2B, thereby exerting regulatory control over the pathogenicity of <i>C. neoformans</i>.
DOI: 10.6084/m9.figshare.30021796.v1
title: Ubiquitin degradation of the Ribonuclease H2 subunit B Rnh2B regulates the virulence of <i>Cryptococcus neoformans</i>

description: The ubiquitin-proteasome system (UPS) regulates protein degradation in eukaryotes by polyubiquitinating substrate proteins, with F-box proteins serving as key components for substrate recognition. Research has shown that the absence of Cdc4, an F-box protein in <i>C. neoformans</i>, decreases virulence, yet the mechanisms by which Cdc4 affects these processes remain unclear. Using an iTRAQ-based proteomic strategy, we recognized Ribonuclease H2 subunit B (Rnh2B) as a target substrate for Cdc4. Protein-protein interaction assays have confirmed the interaction between Cdc4 and Rnh2B, indicating that Cdc4 regulates Rnh2B stability through ubiquitination. Functional analyses revealed that both the knockout and overexpression of <i>RNH2B</i> impair growth at 37°C, with the latter also affecting cellular membrane integrity and growth under osmotic stress conditions. Pathogenicity assays revealed that the deletion of <i>RNH2B</i> results in reduced virulence, whereas its overexpression leads to a complete loss of pathogenicity. Longitudinal tracking of fungal infection progression illustrated that mice lungs infected with <i>rnh2B</i>Δ mutants maintained a low yet stable fungal burden, in contrast to a significant reduction in fungal load observed in conjunction with <i>RNH2B</i> overexpression, ultimately leading to complete clearance. Analysis of host immune responses indicated a correlation between diminished virulence in the <i>RNH2B</i><sup>OE</sup> strain and robust host immune activation. Notably, both the <i>RNH2B</i><sup>OE</sup> strain and the <i>cdc4</i>Δ mutant induced analogous adaptive immune responses, facilitating the clearance of <i>C. neoformans</i> infection. Collectively, our findings propose a model wherein Cdc4 mediates the ubiquitination and degradation of Rnh2B, thereby exerting regulatory control over the pathogenicity of <i>C. neoformans</i>.
DOI: 10.6084/m9.figshare.30764565
title: Chronic viral infections impaired the growth process of splenic B cells by upregulating Bbc3 and Atf3 in LCMV-CL13 infected mouse model

description: Chronic persistent viral infections can lead to significant spleen damage, thus disrupting the host humoral immune response; however, the underlying mechanisms remain unclear. In this study, we employed a Lymphocytic choriomeningitis virus (LCMV) chronic infection model to investigate the effects of virus infection on spleen damage. Mice infected with Lymphocytic choriomeningitis virus clone 13 (LCMV-CL13) presented a series of pathological features, such as white pulp atrophy and reduced germinal center diameter, length, and area in the spleen. More importantly, we observed a diminished GC response alongside a weak antibody response in the chronic infection model. Single-cell RNA sequencing (scRNA-seq) further revealed the dysregulation of gene expression, including <i>Bbc3</i>, <i>Atf3</i>, and <i>Ptpn6</i>, which inhibit B-cell differentiation during chronic viral infection. We verify that the upregulation of <i>Bbc3</i> or <i>Atf3</i>, respectively, can promote apoptosis in BaF3 cells. Immune repertoire (IR) analysis revealed that the molecular diversity of the BCR repertoire after LCMV-CL13 infection, specifically manifested in BCR clonal diversity, <i>IGHV</i> gene segment usage preference, and CDR3 sequence changes. In conclusion, this study demonstrated that chronic LCMV-CL13 infection interrupted the development of splenic B cells by increasing the expression of apoptosis genes, thus enhancing our understanding of the underlying mechanisms of B-cell development interruption during chronic viral infection.