Additional file 1 of ApoE4 associated with severe COVID-19 outcomes via downregulation of ACE2 and imbalanced RAS pathway
Bibliographic record
Abstract
Additional file 1: Fig. S1. Expression of ApoE and ACE2 in vitro. Representative western blotting analysis of the ApoE and ACE2 protein levels in A549, HEK-293T, SH-SY5Y, and HUVECs; the data are shown as the mean ± SD of three independent experiments. α-Tubulin was used as a loading control. P values were calculated using one-way ANOVA, *p < 0.05; **p < 0.01; ***p <0.001. Fig. S2. Molecular docking and simulation analyses of the interaction between ApoE and ACE2. A Molecular docking simulation of the SARS-CoV-2 RBD interacting with ACE2 (the orange region of the ACE2 protein represents the region that binds to the spike S1 protein). B and C Plot of backbone RMSD versus time (ns) for ApoE and ACE2. D Plot of Rg versus time (ns) for ApoE-ACE2. E Plot of total SASA versus time (ns) for ApoE-ACE2 complexes. F Number of hydrogen bonds between ApoE and ACE2. G Number of hydrophobic interactions between ApoE and ACE2. H Interaction energy between ACE2 and ApoE. Brown: ApoE2-ACE2, Green: ApoE3-ACE2 and Blue: ApoE4-ACE2. Fig. S3. ApoE4 downregulates ACE2 protein expression in vivo. ACE2 protein levels in the cortex, hippocampus, liver, bowel, spleen, kidney, heart and lung of ApoE2-TR, ApoE3-TR, and ApoE4-TR mice were assessed by immunofluorescence staining. The results were normalized to the expression of a-tubulin. n = 6 mice per group. The sections were stained with an anti-ACE2 (green) antibody and counterstained with DAPI (blue). The data are expressed as the mean ± SD. Statistical differences were evaluated by one-way ANOVA. Scale bars, 100 μm. *p < 0.05; **p < 0.01; ***p <0.001. Fig. S4. ApoE4 regulates Ang II and Ang 1-7 protein expression in vitro. Expression of the Ang II A and Ang 1-7 B proteins in HEK-293T cells as shown by ELISA after transfection with 1 µg/ml Flag, ApoE2-Flag, ApoE3-Flag or ApoE4-Flag plasmids for 48 h. The data are expressed as the mean ± SD. One-way ANOVA tests were used. *p<0.05. Table S1. Characteristics of the included studies. Table S2. Newcastle-Ottawa Scale to assess quality of the involved studies. Table S3. Kinetic parameters of ApoE and ACE2 calculated by BLI. Table S4. Kinetic parameters of ApoE and SARS-CoV-2 (RBD) calculated by BLI.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.019 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.868 | 0.136 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".