Genetic and immunological insights into COVID-19 with acute myocardial infarction: Integrated analysis of mendelian randomization, transcriptomics, and clinical samples

Background: Globally, most deaths result from cardiovascular diseases, particularly ischemic heart disease. COVID-19 affects the heart, worsening existing heart conditions and causing myocardial injury. The mechanistic link between COVID-19 and acute myocardial infarction (AMI) is still being investigated to elucidate the underlying molecular perspectives. Methods: Genetic risk assessment was conducted using two-sample Mendelian randomization (TSMR) to determine the causality between COVID-19 and AMI. Weighted gene co-expression network analysis (WGCNA) and machine learning were used to discover and validate shared hub genes for the two diseases using bulk RNA sequencing (RNA-seq) datasets. Additionally, gene set enrichment analysis (GSEA) and single-cell RNA-seq (scRNA-seq) analyses were performed to characterize immune cell infiltration, communication, and immune correlation of the hub genes. To validate the findings, the expression patterns of hub genes were confirmed in clinical blood samples collected from COVID-19 patients with AMI. Results: TSMR did not find evidence supporting a causal association between COVID-19 or severe COVID-19 and AMI. In the bulk RNA-seq discovery cohorts for both COVID-19 and AMI, WGCNA’s intersection analysis and machine learning identified TLR4 and ABCA1 as significant hub genes, demonstrating high diagnostic and predictive value in the RNA-seq validation cohort. Single-gene GSEA and single-sample GSEA (ssGSEA) revealed immune and inflammatory roles for TLR4 and ABCA1, linked to various immune cell infiltrations. Furthermore, scRNA-seq analysis unveiled significant immune dysregulation in COVID-19 patients, characterized by altered immune cell proportions, phenotypic shifts, enhanced cell-cell communication, and elevated TLR4 and ABCA1 in CD16 monocytes. Lastly, the increased expression of TLR4, but not ABCA1, was validated in clinical blood samples from COVID-19 patients with AMI. Conclusion: No genetic causal link between COVID-19 and AMI and dysregulated TLR4 and ABCA1 may be responsible for the development of immune and inflammatory responses in COVID-19 patients with AMI

Determination of key enzymes for threonine synthesis through in vitro metabolic pathway analysis

Figure S1. The pathway flux (J) in the in vitro system when one enzyme concentration was increased. (A) The pathway flux when purified ThrA was added to the crude enzyme extract. (B) The pathway flux when purified Asd was added to the crude enzyme extract. (C) The pathway flux when purified ThrB was added to the crude enzyme extract. (D) The pathway flux when purified ThrC was added to the crude enzyme extract

Genetic and immunological insights into COVID-19 with acute myocardial infarction: integrated analysis of mendelian randomization, transcriptomics, and clinical samples

BackgroundGlobally, most deaths result from cardiovascular diseases, particularly ischemic heart disease. COVID-19 affects the heart, worsening existing heart conditions and causing myocardial injury. The mechanistic link between COVID-19 and acute myocardial infarction (AMI) is still being investigated to elucidate the underlying molecular perspectives.MethodsGenetic risk assessment was conducted using two-sample Mendelian randomization (TSMR) to determine the causality between COVID-19 and AMI. Weighted gene co-expression network analysis (WGCNA) and machine learning were used to discover and validate shared hub genes for the two diseases using bulk RNA sequencing (RNA-seq) datasets. Additionally, gene set enrichment analysis (GSEA) and single-cell RNA-seq (scRNA-seq) analyses were performed to characterize immune cell infiltration, communication, and immune correlation of the hub genes. To validate the findings, the expression patterns of hub genes were confirmed in clinical blood samples collected from COVID-19 patients with AMI.ResultsTSMR did not find evidence supporting a causal association between COVID-19 or severe COVID-19 and AMI. In the bulk RNA-seq discovery cohorts for both COVID-19 and AMI, WGCNA’s intersection analysis and machine learning identified TLR4 and ABCA1 as significant hub genes, demonstrating high diagnostic and predictive value in the RNA-seq validation cohort. Single-gene GSEA and single-sample GSEA (ssGSEA) revealed immune and inflammatory roles for TLR4 and ABCA1, linked to various immune cell infiltrations. Furthermore, scRNA-seq analysis unveiled significant immune dysregulation in COVID-19 patients, characterized by altered immune cell proportions, phenotypic shifts, enhanced cell-cell communication, and elevated TLR4 and ABCA1 in CD16 monocytes. Lastly, the increased expression of TLR4, but not ABCA1, was validated in clinical blood samples from COVID-19 patients with AMI.ConclusionNo genetic causal link between COVID-19 and AMI and dysregulated TLR4 and ABCA1 may be responsible for the development of immune and inflammatory responses in COVID-19 patients with AMI

The response of grassland mycorrhizal fungal abundance to a range of long-term grazing intensities

Keystone root symbiotic arbuscular mycorrhizal fungi play a major role in maintaining plant biodiversity, increasing plant productivity and enhancing storage of carbon in soil. AM fungi are ubiquitous and found in most ecosystems including grasslands currently experiencing increasing pressures form human activity. Grazing is known to impact AM fungi but very little is known about how AM fungi are affected by different levels of grazing intensity. Here we report on results from a long-term experimental site in a typical steppe in the north of China, containing seven levels of field-manipulated grazing intensities maintained for over 13 years. We assessed arbuscular mycorrhizal fungal abundance, represented by soil hyphal length density and mycorrhizal root colonization (mycorrhizal root frequency, intensity and arbuscule intensity) within the farm-scale field experiment. We also measured environmental variables to explain the responses of mycorrhizal fungi to grazing intensity. Our results showed that with an increase in grazing intensity, soil hyphal length density linearly decreased. There was, however, no significant trend for mycorrhizal root colonization variables in relation to grazing intensity. Mycorrhizal root frequency was negatively correlated with topographic-induced changes in soil nitrogen and phosphorus, while arbuscule intensity was marginally negatively correlated with soil available phosphorus. Further, we found a possible hump-shaped relationship between the ratio of external to internal AM fungal structures and grazing intensity. Our finding showed that external AM fungal structure was clearly impacted by grazing intensity but that this was not the case for internal mycorrhizal structures. This indicated that mycorrhizal functioning was impacted by the intensity of grazing as the mycorrhizal structures responded differently. Indeed the ratio of the foraging extra-radical mycorrhizal hyphae to intra-radical mycorrhizal structures was highest at moderate grazing intensity but strongly decreased by high grazing intensity. Our study suggests that the impacts of grazing intensity on the plant-AMF association could lead to further knock-on effects on the plant-soil system via the feedbacks that exist between plant and AMF communities

Volcanic Age and Geochemistry of the Permian Linxi Formation in Northeast China: Implications for the Tectonic Evolution of the Paleo-Asian Ocean

The tectonic evolution of the Paleo-Asian Ocean (PAO) has been well studied, including its gradual narrowing and closure by subduction. However, aspects of the tectonic evolution of the oceanic domain remain unclear, including the exact timing and nature of the closure. The Central Asian Orogenic Belt (CAOB) was formed by the closure of the PAO and, therefore, contains information about the tectonic evolution of the oceanic domain. Here, we report a study of the petrology, geochronology, and geochemistry of the Taohaiyingzi section of the Permian Linxi Formation in Alukhorqin Banner (Northeast China) in the central part of the CAOB. A newly discovered andesitic tuff from the lower part of the Linxi Formation yields a weighted mean 206Pb/238U age of 262.2 ± 1.1 Ma (n = 87), indicating that the lower part of the Linxi Formation of the Taohaiyingzi section was deposited during the late Guadalupian. Provenance weathering indicators show that the sedimentary rocks of the Linxi Formation are of low maturity. Element geochemical characteristics indicate that the Linxi Formation clastic rocks were derived from eroded magmatic rocks that formed in a continental arc setting and were deposited close to the arc in a continental arc basin environment. The active margin setting was generated by the subduction of the paleo-Asian oceanic plate beneath the Xilinhot–Songliao block. The inferred palaeosalinity of the sedimentary environment changed gradually from brackish to fresh water, suggesting the end of oceanic plate subduction during the late Guadalupian, and the closure of the PAO during or after the Lopingian

Microbial diversity and community composition of fecal microbiota in dual-purpose and egg type ducks

IntroductionDucks are important agricultural animals, which can be divided into egg and dual-purpose type ducks according to economic use. The gut microbiota of ducks plays an important role in their metabolism, immune regulation, and health maintenance.MethodsHere, we use 16S rDNA V4 hypervariable amplicon sequencing to investigate the compositions and community structures of fecal microbiota between egg (five breeds, 96 individuals) and dual-purpose type ducks (four breeds, 73 individuals) that were reared under the same conditions.ResultsThe alpha diversity of fecal microflora in egg type ducks was significantly higher than that in dual-type ducks. In contrast, there is no significant difference in the fecal microbial community richness between the two groups. MetaStat analysis showed that the abundance of Peptostreptococcaceae, Streptococcaceae, Lactobacillus, Romboutsia, and Campylobacter were significantly different between the two groups. The biomarkers associated with the egg and dual-purpose type ducks were identified using LEfSe analysis and IndVal index. Function prediction of the gut microbiota indicated significant differences between the two groups. The functions of environmental information processing, carbohydrate metabolism, lipid metabolism, xenobiotic biodegradation and metabolism, and metabolism of terpenoids and polyketides were more abundant in egg type ducks. Conversely, the genetic information processing, nucleotide metabolism, biosynthesis of amino acids and secondary metabolites, glycan biosynthesis and metabolism, fatty acid elongation, and insulin resistance were significantly enriched in dual-purpose type ducks.DiscussionThis study explored the structure and diversity of the gut microbiota of ducks from different economic-use groups, and provides a reference for improving duck performance by using related probiotics in production

Integrated network analysis and metabolomics reveal the molecular mechanism of Yinchen Sini decoction in CCl4-induced acute liver injury

Objective: Yinchen Sini decoction (YCSND), a traditional Chinese medicine (TCM) formula, plays a crucial role in the treatment of liver disease. However, the bioactive constituents and pharmacological mechanisms of action remain unclear. The present study aimed to reveal the molecular mechanism of YCSND in the treatment of acute liver injury (ALI) using integrated network analysis and metabolomics.Methods: Ultra-high-performance liquid chromatography coupled with Q-Exactive focus mass spectrum (UHPLC-QE-MS) was utilized to identify metabolites in YCSND, and high-performance liquid chromatography (HPLC) was applied to evaluate the quality of four botanical drugs in YCSND. Cell damage and ALI models in mice were established using CCl4. 1H-NMR metabolomics approach, along with histopathological observation using hematoxylin and eosin (H&E), biochemical measurements, and reverse transcription quantitative real-time PCR (RT-qPCR), was applied to evaluate the effect of YCSND on CCl4- induced ALI. Network analysis was conducted to predict the potential targets of YCSND in ALI.Result: Our results showed that 89 metabolites in YCSND were identified using UHPLC-QE-MS. YCSND protected against ALI by reducing the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA) contents and increasing those of superoxide dismutase (SOD), and glutathione (GSH) both in vivo and in vitro. The 1H-NMRmetabolic pattern revealed that YCSND reversed CCl4-induced metabolic abnormalities in the liver. Additionally, the Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis identified five pathways related to liver injury, including the PI3K-AKT, MAPK, HIF-1, apoptosis, and TNF signaling pathways. Moreover, RT-qPCR showed YCSND regulated the inflammatory response (Tlr4, Il6, Tnfα, Nfκb1, Ptgs2, and Mmp9) and apoptosis (Bcl2, Caspase3, Bax, and Mapk3), and inhibited PI3K-AKT signaling pathway (Pi3k and Akt1). Combined network analysis and metabolomics showed a link between the key targets (Tlr4, Ptgs2, and Mmp9) and vital metabolites (choline, xanthine, lactate, and 3-hydroxybutyric acid) of YCSND in ALI.Conclusion: Overall, the results contribute to the understanding of the therapeutic effects of YCSND on ALI, and indicate that the integrated network analysis and metabolomics could be a powerful strategy to reveal the pharmacological effects of TCM

Variation in carbon isotope discrimination in Cleistogenes squarrosa (Trin.) Keng: patterns and drivers at tiller, local, catchment, and regional scales

Understanding the patterns and drivers of carbon isotope discrimination in C4 species is critical for predicting the effects of global change on C3/C4 ratio of plant community and consequently on ecosystem functioning and services. Cleistogenes squarrosa (Trin.) Keng is a dominant C4 perennial bunchgrass of arid and semi-arid ecosystems across the Mongolian plateau of the Eurasian steppe. Its carbon isotope discrimination (13Δ) during photosynthesis is relatively large among C4 species and it is variable. Here the 13Δ of C. squarrosa and its potential drivers at a nested set of scales were examined. Within cohorts of tillers, 13Δ of leaves increased from 5.1‰ to 8.1‰ from old to young leaves. At the local scale, 13Δ of mature leaves varied from 5.8‰ to 8.4‰, increasing with decreasing grazing intensity. At the catchment scale, 13Δ of mature leaves varied from 6.2‰ to 8.5‰ and increased with topsoil silt content. At the regional scale, 13Δ of mature leaves varied from 5.5‰ to 8.9‰, increasing with growing-season precipitation. At all scales, 13Δ decreased with increasing leaf nitrogen content (Nleaf). Nleaf was positively correlated with grazing intensity and leaf position along tillers, but negatively correlated with precipitation. The presence of the correlations across a range of different environmental contexts strongly implicates Nleaf as a major driver of 13Δ in C. squarrosa and, possibly, other C4 species