Table_1_The intricate dance: host autophagy and Coxiella burnetii infection.DOCX

Q fever is a zoonotic disease caused by Coxiella burnetii, an obligatory intracellular bacterial pathogen. Like other intracellular pathogens, C. burnetii is able to survive and reproduce within host cells by manipulating host cellular processes. In particular, the relationship between C. burnetii infection and host autophagy, a cellular process involved in degradation and recycling, is of great interest due to its intricate nature. Studies have shown that autophagy can recognize and target intracellular pathogens such as Legionella and Salmonella for degradation, limiting their replication and promoting bacterial clearance. However, C. burnetii can actively manipulate the autophagic pathway to create an intracellular niche, known as the Coxiella-containing vacuole (CCV), where it can multiply and evade host immune responses. C. burnetii promotes the fusion of CCVs with lysosomes through mechanisms involving virulence factors such as Cig57 and CvpF. This review summarizes the latest findings on the dynamic interaction between host autophagy and C. burnetii infection, highlighting the complex strategies employed by both the bacterium and the host. A better understanding of these mechanisms could provide important insights into the development of novel therapeutic interventions and vaccine strategies against C. burnetii infections.</p

Additional file 1 of MetaRNN: differentiating rare pathogenic and rare benign missense SNVs and InDels using deep learning

Additional file 1: Includes 11 tables for training and testing data sets used in the study. The names of the tables are: Table S1. Training variants for MetaRNN; Table S2. Training variants for MetaRNN-indel; Table S3. Summary statistics for test datasets used to evaluate MetaRNN; Table S4. RNTS validation data set for MetaRNN model evaluation; Table S5. RCTS validation data set for MetaRNN model evaluation; Table S6. AF-RNTS validation data set for MetaRNN model evaluation; Table S7. AAFS validation data set for MetaRNN model evaluation; Table S8. TP53 validation data set for MetaRNN model evaluation; Table S9. Cancer somatic hotspot validation data set for MetaRNN model evaluation; Table S10. ClinVar validation data set for MetaRNN-indel model evaluation; Table S11. Search space of hyperparameters for MetaRNN and MetaRNN-indel

Effects of <i>n</i>‑Butane Coverage on Its Catalytic Dehydrogenation: A Density Functional Theory Study on the Pt(111) Surface

Butane dehydrogenation at different butane coverages on the Pt(111) surface have been investigated using density functional theory (DFT) calculations. The adsorption of intermediates on the surface with a lower coverage is stronger, resulting in a more facile activation of C–H. Based on the microkinetic model, it was found that the coverage has a strong influence on the reaction activity but no obvious effect on the reaction pathway. Analysis of the degree of rate control reveals that the rate-determining steps for each product are similar at different coverages. Furthermore, at lower coverage, the energy barrier for butadiene desorption is higher than that for the preceding C–H bond cleavage step, resulting in deeper dehydrogenation. Moreover, C–C bond cleavage was found to primarily occur from the products obtained from deep dehydrogenation of butadiene. Our results help to interpret experimental butane dehydrogenation and provide ways to improve catalyst performance

Additional file 2 of MetaRNN: differentiating rare pathogenic and rare benign missense SNVs and InDels using deep learning

Additional file 2: Includes 9 figures of additional results. The names of the figures are: Figure S1. Performance (AUC) of different methods benchmarked using the rare nsSNV test set (RNTS, test set 1); Figure S2. Performance (AUC) of different methods benchmarked using the de-novo rare ClinVar test set (DN-RCTS, test set 3); Figure S3. Performance (precision-recall curve) of different methods benchmarked using the de-novo rare ClinVar test set (DN-RCTS, test set 3); Figure S4. Performance (AUC vs. average precision-recall) of different methods benchmarked using the rare ClinVar test set (RCTS, test set 2); Figure S5. Performance (AUC) of different methods benchmarked using the all-allele-frequency set (AAFS, test set 4) ; Figure S6. Performance (AUC) of different methods benchmarked using DM nsSNVs from HGMD and rare variants from gnomAD (test set 7); Figure S7. Performance (AUC) of different methods benchmarked using TP53 test set (TP53TS, test set 5); Figure S8. Performance (AUC) of different methods benchmarked using cancer somatic hotspot mutations as TPs and population sequencing mutations from DiscovEHR as TNs (test set 6); Figure S9. Pooled analysis of MetaRNN and MetaRNN-indel predictions

DataSheet_3_Tea intake and lung diseases: a Mendelian randomization study.doc

BackgroundExisting studies on the relationship between tea intake and lung diseases have yielded inconsistent results, leading to an ongoing dispute on this issue. The impact of tea consumption on the respiratory system remained elucidating.Materials and methodsWe conducted a two-sample Mendelian randomization (MR) study to evaluate the associations between five distinct tea intake phenotypes and 15 different respiratory outcomes using open Genome-wide association study (GWAS) data. The inverse variance weighted (IVW) was used for preliminary screening and a variety of complementary methods were used as sensitivity analysis to validate the robustness of MR estimates. Pathway enrichment analysis was used to explore possible mechanisms.ResultsIVW found evidence for a causal effect of standard tea intake on an increased risk of lung squamous cell cancer (LSCC) (OR = 1.004; 95% CI = 1.001–1.007; P = 0.00299). No heterogeneity or pleiotropy was detected. After adjustment for potential mediators, including smoking, educational attainment, and time spent watching television, the association was still robust in multivariable MR. KEGG and GO enrichment predicted proliferation and activation of B lymphocytes may play a role in this causal relation. No causalities were observed when evaluating the effect of other kinds of tea intake on various pulmonary diseases.ConclusionOur MR estimates provide causal evidence of the independent effect of standard tea intake (black tea intake) on LSCC, which may be mediated by B lymphocytes. The results implied that the population preferring black tea intake should be wary of a higher risk of LSCC.</p

Imine Resveratrol Analogues: Molecular Design, Nrf2 Activation and SAR Analysis

<div><p>Resveratrol is a natural phenol with protective effects against cancer and inflammation-related diseases. Its mechanism of action involves the activation of nuclear factor E2 p45-related factor 2 (Nrf2), which plays a key role in regulation of genes driven by antioxidant response element (ARE). Inspired by the effect of resveratrol, here we synthesized a series of imine resveratrol analogs (IRAs), evaluated their abilities to activate Nrf2 by using cell based ARE-reporter assay. After the first-round screening, preliminary and quantitative structure-activity relationship (SAR) was analyzed, and the structural features determining Nrf2 activation ability were proposed. Two novel IRAs were designed and subsequently synthesized, namely 2-methoxyl-3,6-dihydroxyl-IRA and 2,3,6-trihydroxyl-IRA. They were proved to be the most potent Nrf2 activators among the IRAs.</p></div

Structures (A) and ARE-luciferase activities (B) of 33, 34 and resveratrol.

<p>ARE reporter cells were exposed to <b>33</b>, <b>34</b> and resveratrol (7.5 µM, 15 µM and 30 µM) for 24 h. The value for cells treated with vehicle DMSO (0.1% v/v) was set at 1. Results are from three separate experiments. Values shown are mean ± SD.</p

Synthesized IRAs and their effects on ARE-luciferase activity.

<p>ARE reporter cells were exposed to 7.5 µM, 15 µM or 30 µM IRA for 24 h. The value for cells treated with vehicle DMSO (0.1% v/v) was set at 1. Results are from three separate experiments.</p>a<p>Due to cytotoxicity of <b>9</b>.</p

SAR results from initial screening of IRAs.

<p>SAR results from initial screening of IRAs.</p

Image_1_Tea intake and lung diseases: a Mendelian randomization study.tif

BackgroundExisting studies on the relationship between tea intake and lung diseases have yielded inconsistent results, leading to an ongoing dispute on this issue. The impact of tea consumption on the respiratory system remained elucidating.Materials and methodsWe conducted a two-sample Mendelian randomization (MR) study to evaluate the associations between five distinct tea intake phenotypes and 15 different respiratory outcomes using open Genome-wide association study (GWAS) data. The inverse variance weighted (IVW) was used for preliminary screening and a variety of complementary methods were used as sensitivity analysis to validate the robustness of MR estimates. Pathway enrichment analysis was used to explore possible mechanisms.ResultsIVW found evidence for a causal effect of standard tea intake on an increased risk of lung squamous cell cancer (LSCC) (OR = 1.004; 95% CI = 1.001–1.007; P = 0.00299). No heterogeneity or pleiotropy was detected. After adjustment for potential mediators, including smoking, educational attainment, and time spent watching television, the association was still robust in multivariable MR. KEGG and GO enrichment predicted proliferation and activation of B lymphocytes may play a role in this causal relation. No causalities were observed when evaluating the effect of other kinds of tea intake on various pulmonary diseases.ConclusionOur MR estimates provide causal evidence of the independent effect of standard tea intake (black tea intake) on LSCC, which may be mediated by B lymphocytes. The results implied that the population preferring black tea intake should be wary of a higher risk of LSCC.</p