Sox17 Mediated Regeneration of the Lung Endothelium Following Acute Lung Injury

Repair of the endothelial cell barrier after inflammatory injury is essential for tissue fluid homeostasis and normalizing leukocyte transmigration. However, the mechanisms of endothelial regeneration remain poorly understood. Here I show that the endothelial and hematopoietic developmental transcription factor Sox17 promotes endothelial regeneration in the endotoxemia model of endothelial injury. Genetic lineage tracing studies demonstrate that the native endothelium itself serves as the primary source of endothelial cells repopulating the vessel wall following injury. I identify Sox17 as a key regulator of endothelial cell regeneration using endothelial-specific deletion and overexpression of Sox17. Endotoxemia upregulates Hypoxia inducible factor 1α, which in turn transcriptionally activates Sox17 expression. I observe that Sox17 increases endothelial cell proliferation via upregulation of Cyclin E1. Furthermore, endothelial-specific upregulation of Sox17 in vivo enhances lung endothelial regeneration. I conclude that endotoxemia adaptively activates Sox17 expression to mediate Cyclin E1-dependent endothelial cell regeneration and restore vascular homeostasis

A Unified Approach to Derive Atomic Partial Charges and Polarizabilities of Ionic Liquids

We propose a unified approach to fit simultaneously a set of atomic partial charges and polarizabilities of the polarizable model against the ab initio electrostatic potential (ESP) and polarizability. The polarizable model is represented with interactive atomic dipoles with distance-dependent attenuation. For the polarizable model employed in this study, the internal electric field on the polarization sites is fully turned on, and thus allows self-induced dipoles, which persist even for an isolated molecule/ion. By such treatment, the contribution of ESP stems not only from the partial charges but also from the self-induced dipoles, and the atomic partial charges and polarizabilities can be fitted simultaneously against ESP in a unified manner. The fitting with 1-ethyl-3-methylimidazolium (EMIM+) and nitrate (NO3–), a prototypical organic cation and inorganic anion, respectively, that can form ionic liquid, demonstrates that allowance of the self-induced dipoles gives much better fitness. Moreover, test on the total dipole of an EMIM+/NO3– ion pair shows that the agreement with the ab initio dipole is also much improved for the polarizable model, which highlights the importance of the polarization effects of ionic liquids

A Unified Approach to Derive Atomic Partial Charges and Polarizabilities of Ionic Liquids

We propose a unified approach to fit simultaneously a set of atomic partial charges and polarizabilities of the polarizable model against the ab initio electrostatic potential (ESP) and polarizability. The polarizable model is represented with interactive atomic dipoles with distance-dependent attenuation. For the polarizable model employed in this study, the internal electric field on the polarization sites is fully turned on, and thus allows self-induced dipoles, which persist even for an isolated molecule/ion. By such treatment, the contribution of ESP stems not only from the partial charges but also from the self-induced dipoles, and the atomic partial charges and polarizabilities can be fitted simultaneously against ESP in a unified manner. The fitting with 1-ethyl-3-methylimidazolium (EMIM+) and nitrate (NO3–), a prototypical organic cation and inorganic anion, respectively, that can form ionic liquid, demonstrates that allowance of the self-induced dipoles gives much better fitness. Moreover, test on the total dipole of an EMIM+/NO3– ion pair shows that the agreement with the ab initio dipole is also much improved for the polarizable model, which highlights the importance of the polarization effects of ionic liquids

DataSheet2_Effect of adjuvant therapy with compound danshen drip pill on inflammatory factors and cardiac function after percutaneous coronary intervention for acute myocardial infarction: a systematic review and meta-analysis.docx

Objectives: The purpose of the study was to comprehensively evaluate efficacy and safety of CDDP in patients with AMI undergoing PCI.Methods: A computerised search was conducted on the CNKI, WF, VIP, CBM, PubMed, Embase, Web of Science, and Cochrane Library databases for RCTs of CDDP adjuvant therapy for AMI up to May 2023. STATA 17.0 was used to perform meta-analyses, sensitivity analyses, subgroup analyses, meta-regression, and publication bias assessments. TSA 0.9.5.10 Beta was used for trial sequential analysis (TSA). Evidence confidence of meta results was evaluated by GRADE (Grading of Recommendations Assessment, Development and Evaluation) according to the instructions.Results: The results of the meta-analysis showed that CDDP combined with conventional western treatment (CWT) was superior to CWT in increasing LVEF and TCER and decreasing LVEDD, hs-CRP, IL-6 and TNF-α. The quality of evidence for TCER was moderate, LVEF, LVEDD, IL-6, and TNF-α were low. The TSA results showed that the total number of samples collected in this study met the requirements for meta-analysis and excluded the possibility of false positives, further confirming the efficacy of CDDP for the treatment of AMI undergoing PCI.Conclusion: Adjuvant treatment of AMI with CDDP has shown exciting and safe benefits in improving cardiac function and reducing inflammatory response in patients with AMI undergoing PCI, but the quality of some of the included studies was poor, and the results should be interpreted with caution until further confirmation by well-designed RCTs.Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/#recordDetails], identifier [CRD42023453293].</p

Table1_Effect of adjuvant therapy with compound danshen drip pill on inflammatory factors and cardiac function after percutaneous coronary intervention for acute myocardial infarction: a systematic review and meta-analysis.docx

Objectives: The purpose of the study was to comprehensively evaluate efficacy and safety of CDDP in patients with AMI undergoing PCI.Methods: A computerised search was conducted on the CNKI, WF, VIP, CBM, PubMed, Embase, Web of Science, and Cochrane Library databases for RCTs of CDDP adjuvant therapy for AMI up to May 2023. STATA 17.0 was used to perform meta-analyses, sensitivity analyses, subgroup analyses, meta-regression, and publication bias assessments. TSA 0.9.5.10 Beta was used for trial sequential analysis (TSA). Evidence confidence of meta results was evaluated by GRADE (Grading of Recommendations Assessment, Development and Evaluation) according to the instructions.Results: The results of the meta-analysis showed that CDDP combined with conventional western treatment (CWT) was superior to CWT in increasing LVEF and TCER and decreasing LVEDD, hs-CRP, IL-6 and TNF-α. The quality of evidence for TCER was moderate, LVEF, LVEDD, IL-6, and TNF-α were low. The TSA results showed that the total number of samples collected in this study met the requirements for meta-analysis and excluded the possibility of false positives, further confirming the efficacy of CDDP for the treatment of AMI undergoing PCI.Conclusion: Adjuvant treatment of AMI with CDDP has shown exciting and safe benefits in improving cardiac function and reducing inflammatory response in patients with AMI undergoing PCI, but the quality of some of the included studies was poor, and the results should be interpreted with caution until further confirmation by well-designed RCTs.Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/#recordDetails], identifier [CRD42023453293].</p

DataSheet1_Effect of adjuvant therapy with compound danshen drip pill on inflammatory factors and cardiac function after percutaneous coronary intervention for acute myocardial infarction: a systematic review and meta-analysis.PDF

Objectives: The purpose of the study was to comprehensively evaluate efficacy and safety of CDDP in patients with AMI undergoing PCI.Methods: A computerised search was conducted on the CNKI, WF, VIP, CBM, PubMed, Embase, Web of Science, and Cochrane Library databases for RCTs of CDDP adjuvant therapy for AMI up to May 2023. STATA 17.0 was used to perform meta-analyses, sensitivity analyses, subgroup analyses, meta-regression, and publication bias assessments. TSA 0.9.5.10 Beta was used for trial sequential analysis (TSA). Evidence confidence of meta results was evaluated by GRADE (Grading of Recommendations Assessment, Development and Evaluation) according to the instructions.Results: The results of the meta-analysis showed that CDDP combined with conventional western treatment (CWT) was superior to CWT in increasing LVEF and TCER and decreasing LVEDD, hs-CRP, IL-6 and TNF-α. The quality of evidence for TCER was moderate, LVEF, LVEDD, IL-6, and TNF-α were low. The TSA results showed that the total number of samples collected in this study met the requirements for meta-analysis and excluded the possibility of false positives, further confirming the efficacy of CDDP for the treatment of AMI undergoing PCI.Conclusion: Adjuvant treatment of AMI with CDDP has shown exciting and safe benefits in improving cardiac function and reducing inflammatory response in patients with AMI undergoing PCI, but the quality of some of the included studies was poor, and the results should be interpreted with caution until further confirmation by well-designed RCTs.Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/#recordDetails], identifier [CRD42023453293].</p

Image_1_Lung single-cell RNA profiling reveals response of pulmonary capillary to sepsis-induced acute lung injury.tif

BackgroundSepsis-induced acute lung injury (ALI) poses a significant threat to human health. Endothelial cells, especially pulmonary capillaries, are the primary barriers against sepsis in the lungs. Therefore, investigating endothelial cell function is essential to understand the pathophysiological processes of sepsis-induced ALI.MethodsWe downloaded single-cell RNA-seq expression data from GEO with accession number GSE207651. The mice underwent cecal ligation and puncture (CLP) surgery, and lung tissue samples were collected at 0, 24, and 48 h. The cells were annotated using the CellMarker database and FindAllMarkers functions. GO enrichment analyses were performed using the Metascape software. Gene set enrichment Analysis (GSEA) and variation Analysis (GSVA) were performed to identify differential signaling pathways. Differential expression genes were collected with the “FindMarkers” function. The R package AUCell was used to score individual cells for pathway activities. The Cellchat package was used to explore intracellular communication.ResultsGranulocytes increased significantly as the duration of endotoxemia increased. However, the number of T cells, NK cells, and B cells declined. Pulmonary capillary cells were grouped into three sub-clusters. Capillary-3 cells were enriched in the sham group, but declined sharply in the CLP.24 group. Capillary-1 cells peaked in the CLP.24 group, while Capillary-2 cells were enriched in the CLP.48 group. Furthermore, we found that Cd74+ Capillary-3 cells mainly participated in immune interactions. Plat+ Capillary-1 and Clec1a+ Capillary-2 are involved in various physiological processes. Regarding cell-cell interactions, Plat+ Capillary-1 plays the most critical role in granulocyte adherence to capillaries during ALI. Cd74+ Capillary cells expressing high levels of major histocompatibility complex (MHC) and mainly interacted with Cd8a+ T cells in the sham group.ConclusionPlat+ capillaries are involved in the innate immune response through their interaction with neutrophils via ICAM-1 adhesion during endotoxemia, while Cd74+ capillaries epxressed high level of MHC proteins play a role in adaptive immune response through their interaction with T cells. However, it remains unclear whether the function of Cd74+ capillaries leans towards immunity or tolerance, and further studies are needed to confirm this.</p

DataSheet_1_Lung single-cell RNA profiling reveals response of pulmonary capillary to sepsis-induced acute lung injury.pdf

BackgroundSepsis-induced acute lung injury (ALI) poses a significant threat to human health. Endothelial cells, especially pulmonary capillaries, are the primary barriers against sepsis in the lungs. Therefore, investigating endothelial cell function is essential to understand the pathophysiological processes of sepsis-induced ALI.MethodsWe downloaded single-cell RNA-seq expression data from GEO with accession number GSE207651. The mice underwent cecal ligation and puncture (CLP) surgery, and lung tissue samples were collected at 0, 24, and 48 h. The cells were annotated using the CellMarker database and FindAllMarkers functions. GO enrichment analyses were performed using the Metascape software. Gene set enrichment Analysis (GSEA) and variation Analysis (GSVA) were performed to identify differential signaling pathways. Differential expression genes were collected with the “FindMarkers” function. The R package AUCell was used to score individual cells for pathway activities. The Cellchat package was used to explore intracellular communication.ResultsGranulocytes increased significantly as the duration of endotoxemia increased. However, the number of T cells, NK cells, and B cells declined. Pulmonary capillary cells were grouped into three sub-clusters. Capillary-3 cells were enriched in the sham group, but declined sharply in the CLP.24 group. Capillary-1 cells peaked in the CLP.24 group, while Capillary-2 cells were enriched in the CLP.48 group. Furthermore, we found that Cd74+ Capillary-3 cells mainly participated in immune interactions. Plat+ Capillary-1 and Clec1a+ Capillary-2 are involved in various physiological processes. Regarding cell-cell interactions, Plat+ Capillary-1 plays the most critical role in granulocyte adherence to capillaries during ALI. Cd74+ Capillary cells expressing high levels of major histocompatibility complex (MHC) and mainly interacted with Cd8a+ T cells in the sham group.ConclusionPlat+ capillaries are involved in the innate immune response through their interaction with neutrophils via ICAM-1 adhesion during endotoxemia, while Cd74+ capillaries epxressed high level of MHC proteins play a role in adaptive immune response through their interaction with T cells. However, it remains unclear whether the function of Cd74+ capillaries leans towards immunity or tolerance, and further studies are needed to confirm this.</p

Underlying Mechanisms for the Sex- and Chemical-Specific Hepatotoxicity of Perfluoroalkyl Phosphinic Acids in Common Carp (Cyprinus carpio)

The hepatotoxicities of perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been extensively investigated, while little is known about the sex-specific differences. In this study, common carp were exposed to the emerging perfluoroalkyl phosphinic acids (6:6 and 8:8 PFPiAs) for 14 days to disclose sex-specific hepatotoxicity. Apparent hepatotoxicity, including cell necrosis, apoptosis, and steatosis, was observed in both male and female carp liver. The observed hepatocyte steatosis was predominantly attributed to the dysregulation of hepatic lipid metabolism but was based on sex-specific mechanisms. It was manifested as inhibited oxidative decomposition of fatty acids (FAs) in the female liver, whereas it enhanced the uptake of FAs into the male liver, both of which led to excessive lipid accumulation. Untargeted lipidomics validated that the metabolism pathways of FA, sphingolipid, glycerolipid, and glycerophospholipid were disrupted by both compounds, leading to the generation of reactive oxygen species and oxidative stress. The oxidative stress further evolved into inflammation, manifested as promoted expression of proinflammatory cytokines and repressed expression of anti-inflammatory cytokines. Consistently, all of the changes were more noticeable in male carp, suggesting that male fish were more susceptible to PFPiA disruption. 8:8 PFPiA was less accumulated but caused stronger hepatotoxicity than 6:6 PFPiA, possibly because of the stronger binding capacity of 8:8 PFPiA to nuclear transcription factors mediating lipid metabolism and inflammation. The findings of this study highlight the significance of sex- and chemical-dependent bioaccumulation and the toxicity of PFASs in organisms