Proteins play a pivotal role in coordinating the functions of organisms, essentially governing their traits, as the dynamic arrangement of diverse amino acids leads to a multitude of folded configurations within peptide chains. Despite dynamic changes in amino acid composition of an individual protein (referred to as AAP) and great variance in protein expression levels under different conditions, our study, utilizing transcriptomics data from four model organisms uncovers surprising stability in the overall amino acid composition of the total cellular proteins (referred to as AACell). Although this value may vary between different species, we observed no significant differences among distinct strains of the same species. This indicates that organisms enforce system-level constraints to maintain a consistent AACell, even amid fluctuations in AAP and protein expression. Further exploration of this phenomenon promises insights into the intricate mechanisms orchestrating cellular protein expression and adaptation to varying environmental challenges.
Atherosclerosis is a chronic systemic inflammatory disease that causes severe cardiovascular events. B cell lymphoma 2-associated athanogene (BAG3) was proven to participate in the regulation of tumor angiogenesis, neurodegenerative diseases, and cardiac diseases, but its role in atherosclerosis remains unclear. Here, we aim to investigate the role of BAG3 in atherosclerosis and elucidate the potential molecular mechanism. In this study, ApoE−/− mice were given a tail-vein injection of BAG3-overexpressing lentivirus and fed a 12-week high-fat diet (HFD) to investigate the role of BAG3 in atherosclerosis. The overexpression of BAG3 reduced plaque areas and improved atherosclerosis in ApoE−/− mice. Our research proves that BAG3 promotes autophagy in vitro, contributing to the suppression of EndMT in human umbilical vein endothelial cells (HUVECs). Mechanically, autophagy activation is mediated by BAG3 via the interaction between BAG3 and its chaperones HSP70 and HSPB8. In conclusion, BAG3 facilitates autophagy activation via the formation of the chaperone-assisted selective autophagy (CASA) complex interacting with HSP70 and HSPB8, leading to the inhibition of EndMT during the progression of atherosclerosis and indicating that BAG3 is a potential therapeutic target for atherosclerosis.
Actinomycetes are versatile secondary metabolite producers with great application potential in industries. However, industrial strain engineering has long been limited by the inefficient and labor-consuming plate/flask-based screening process, resulting in an urgent need for product-driven high-throughput screening methods for actinomycetes. Here, we combine a whole-cell biosensor and microfluidic platform to establish the whole-cell biosensor and producer co-cultivation-based microfluidic platform for screening actinomycetes (WELCOME). In WELCOME, we develop an MphR-based Escherichia coli whole-cell biosensor sensitive to erythromycin and co-cultivate it with Saccharopolyspora erythraea in droplets for high-throughput screening. Using WELCOME, we successfully screen out six erythromycin hyper-producing S. erythraea strains starting from an already high-producing industrial strain within 3 months, and the best one represents a 50% improved yield. WELCOME completely circumvents a major problem of industrial actinomycetes, which is usually genetic-intractable, and this method will revolutionize the field of industrial actinomycete engineering.
The objective of this study was to investigate the effects of exercise training on muscle metabolism, fatty acid composition, carcass traits, and meat quality characteristics of Mongolian sheep. Fourteen Mongolian sheep were randomly divided into two groups (7 sheep in each) and placed in two adjacent livestock pens. One group of sheep was kept in the pen (Control [C] group) and the other group of sheep (Training [T] group) were driven away in a field to walk twice a day. The results showed a reduction in pH measured 45 min post mortem, L*, a*, and b* value, intramuscular fat, and carcass length, and an increase in the ultimate pH value and shear force in the meat of T group in comparison with that of C group (p < .050). Also, exercise training moderately affected the fatty acid composition of LT muscle. Compared with C group, the concentrations of myristoleic acid (C14:1) and stearic acid (C18:0) were increased (p < .050), while the concentrations of C20:3 n-6, neurolic acid (C24:1), and n-3 polyunsaturated fatty acid (PUFA) were decreased in T group (p < .050). Transcriptome analysis highlighted 621 genes differentially expressed in two groups, including 385 were up-regulated (e.g., GLUT4 and PGC-1α) and 236 were down-regulated (e.g., PLIN1 and ACSL3) in T with respect to C group. Besides, considering these genes, a number of enrichment pathways related to muscle metabolic processes, involving carbohydrate metabolism, lipid metabolism, oxidation reduction process, and muscle tissue development, were highlighted. In conclusion, these results contributed to a better understanding of the possible biological and molecular processes underlying the effects of exercise training on muscle metabolism and meat quality in Mongolian sheep, and provide useful information for contributing to understand the phenotypic and functional differences in meat quality of sheep.
Abstract Coronavirus disease 2019 (COVID-19) is spreading rapidly around the world. However, the treatment of vitiligo combined with COVID-19 has not been reported. Astragalus membranaceus (AM) has a therapeutic effect on patients with vitiligo and COVID-19. This study aims to discover its possible therapeutic mechanisms and provide potential drug targets. Using the Chinese Medicine System Pharmacological Database (TCMSP), GEO database and Genecards websites and other databases, AM target, vitiligo disease target, and COVID-19 related gene set were established. Then find the crossover genes by taking the intersection. Then use GO, KEGG enrichment analysis, and PPI network to discover its underlying mechanism. Finally, by importing drugs, active ingredients, crossover genes, and enriched signal pathways into Cytoscape software, a “drug-active ingredient-target signal pathway-” network is constructed. TCMSP screened and obtained 33 active ingredients including baicalein (MOL002714), NEOBAICALEIN (MOL002934), Skullcapflavone II (MOL002927), and wogonin (MOL000173), which acted on 448 potential targets. 1166 differentially expressed genes for vitiligo were screened by GEO. CIVID-19 related genes were screened by Genecards. Then by taking the intersection, a total of 10 crossover genes (PTGS2, CDK1, STAT1, BCL2L1, SCARB1, HIF1A, NAE1, PLA2G4A, HSP90AA1, and HSP90B1) were obtained. KEGG analysis found that it was mainly enriched in signaling pathways such as IL-17 signaling pathway, Th17 cell differentiation, Necroptosis, NOD-like receptor signaling pathway. Five core targets (PTGS2, STAT1, BCL2L1, HIF1A, and HSP90AA1) were obtained by analyzing the PPI network. The network of "active ingredients-crossover genes" was constructed by Cytoscape, and the 5 main active ingredients acting on the 5 core crossover genes acacetin, wogonin, baicalein, bis2S)-2-ethylhexyl) benzene-1,2-dicarboxylate and 5,2′-Dihydroxy-6,7,8-trimethoxyflavone. The core crossover genes obtained by PPI and the core crossover genes obtained by the "active ingredient-crossover gene" network are intersected to obtain the three most important core genes (PTGS2, STAT1, HSP90AA1). AM may act on PTGS2, STAT1, HSP90AA1, etc. through active components such as acacetin, wogonin, baicalein, bis2S)-2-ethylhexyl) benzene-1,2-dicarboxylate and 5,2′-Dihydroxy-6,7,8-trimethoxyflavone to activate IL-17 signaling pathway, Th17 cell differentiation, Necroptosis, NOD-like receptor signaling pathway, Kaposi sarcoma-associated herpesvirus infection, and VEGF signaling pathway and other signaling pathways to achieve the effect of treating vitiligo and COVID-19.
Abstract Flux balance analysis (FBA) is an important method for calculating optimal pathways to produce industrially important chemicals in genome-scale metabolic models (GEMs). However, for biologists, the requirement of coding skills poses a significant obstacle to using FBA for pathway analysis and engineering target identification. Additionally, a time-consuming manual drawing process is often needed to illustrate the mass flow in an FBA-calculated pathway, making it challenging to detect errors or discover interesting metabolic features. To solve this problem, we developed CAVE, a cloud-based platform for the integrated calculation, visualization, examination and correction of metabolic pathways. CAVE can analyze and visualize pathways for over 100 published GEMs or user-uploaded GEMs, allowing for quicker examination and identification of special metabolic features in a particular GEM. Additionally, CAVE offers model modification functions, such as gene/reaction removal or addition, making it easy for users to correct errors found in pathway analysis and obtain more reliable pathways. With a focus on the design and analysis of optimal pathways for biochemicals, CAVE complements existing visualization tools based on manually drawn global maps and can be applied to a broader range of organisms for rational metabolic engineering. CAVE is available at https://cave.biodesign.ac.cn/.
Abstract Flavonoids with great medicinal value play an important role in plant individual growth and stress resistance. Flavonol synthetase (FLS) is one of the key enzymes to synthesize flavonoids. However, the role of the FLS gene in flavonoid accumulation and tolerance to abiotic stresses, as well as its mechanism has not yet been investigated systematically in plants. The aim of this research is to evaluate the effect of FLS overexpression on the accumulation of active ingredients and stress resistance in Euphorbia kansui Liou. The results showed that when the EkFLS gene was overexpressed in Arabidopsis thaliana , the accumulation of flavonoids was improved. In addition, when the wild‐type and EkFLS overexpressed Arabidopsis plants were treated with ABA and MeJA, compared with WT Arabidopsis, EkFLS overexpressed Arabidopsis promoted stomatal aperture to influence photosynthesis of the plants, which in turn can promote stress resistance. Meanwhile, under MeJA, NaCl, and PEG treatment, EkFLS overexpressed in Arabidopsis induced higher accumulation of flavonoids, which significantly enhanced peroxidase (POD) and superoxide dismutase (SOD) activities that can scavenge reactive oxygen species in cells to protect the plant. These results indicated that EkFLS overexpression is strongly correlated to the increase of flavonoid synthesis and therefore the tolerance to abiotic stresses in plants, providing a theoretical basis for further improving the quality of medicinal plants and their resistance to abiotic stresses simultaneously.
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