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Frontiers in Plant Science 2024leaves are highly valued in traditional Chinese medicine for their substantial concentration of flavonoids, which play a crucial role in manifesting the plant's...
leaves are highly valued in traditional Chinese medicine for their substantial concentration of flavonoids, which play a crucial role in manifesting the plant's therapeutic properties. This study investigated the metabolomic, transcriptomic and proteomic profiles of leaves from two cultivars, (J) and (R), at three different developmental stages. Metabolite identification and analysis revealed a total of 1,412 and 1,421 metabolites with known structures were found. Flavonoids made up of 33%, including 10 significant accumulated icariin analogues. Transcriptomic analysis unveiled totally 41,644 differentially expressed genes (DEGs) containing five encoded genes participated in icariin biosynthesis pathways. Totally, 9,745 differentially expressed proteins (DEPs) were found, including Cluster-47248.2.p1 (UDP-glucuronosy/UDP-glucosyltransferase), Cluster-30441.2.p1 (O-glucosyltransferase), and Cluster-28344.9.p1 (anthocyanidin 3-O-glucoside 2 "-O-glucosyltransferase-like) through proteomics analysis which are involved to icariin biosynthesis. Protein-protein interaction (PPI) assay exhibited, totally 12 proteins showing a strong relationship of false discovery rate (FDR) <0.05 with these three proteins containing 2 leucine-rich repeat receptor kinase-like protein SRF7, and 5 methyl jasmonate esterase 1. Multi-omics connection networks uncovered 237 DEGs and 72 DEPs exhibited significant associations with the 10 icariin analogues. Overall, our integrated omics approach provides comprehensive insights into the regulatory network underlying icariin synthesis in , offering valuable resources for further research and development in medicinal plant cultivation and pharmaceutical applications.
PubMed: 38933461
DOI: 10.3389/fpls.2024.1409601 -
Frontiers in Cell and Developmental... 2024Endometriosis (EM), characterized by ectopic growth of endometrial tissues and recurrent pelvic pain, is a common disease with severe negative impacts on the life... (Review)
Review
Endometriosis (EM), characterized by ectopic growth of endometrial tissues and recurrent pelvic pain, is a common disease with severe negative impacts on the life quality of patients. Conventional uterine tissue transplantation-based models have been broadly used to investigate the pathogenic mechanism(s) of EM. Transgenic mice with whole body or uterine/pelvic tissue-specific labelling by the expression of GFP, β-gal or other light-emitting or chromogenic markers enable investigators to analyze the contribution to endometriotic lesions by the donor or recipient side after uterine tissue transplantation. Moreover, when coupled to uterine tissue transplantation, transgenic mice with a specific EM-related gene knocked out or overexpressed make it possible to determine the gene's role(s) for EM pathogenesis. Furthermore, observations on the rise of endometriotic lesions as well as structural/functional changes in the eutopic endometrium or pelvic tissues after gene manipulation will directly relate the cognate gene to the onset of EM. A major advantage of transgenic EM models is their efficiency for analyzing gene interactions with hormonal, dietetic and/or environmental factors. This review summarizes the features/sources/backgrounds of transgenic mice and their applications to EM studies concerning hormonal regulation, angiogenesis and inflammation. Findings from these studies, the advantages/disadvantages of transgenic EM models, and future expectations are also discussed.
PubMed: 38933332
DOI: 10.3389/fcell.2024.1376414 -
Fundamental Research Sep 2023RNA molecules serve a wide range of functions that are closely linked to their structures. The basic structural units of RNA consist of single- and double-stranded... (Review)
Review
RNA molecules serve a wide range of functions that are closely linked to their structures. The basic structural units of RNA consist of single- and double-stranded regions. In order to carry out advanced functions such as catalysis and ligand binding, certain types of RNAs can adopt higher-order structures. The analysis of RNA structures has progressed alongside advancements in structural biology techniques, but it comes with its own set of challenges and corresponding solutions. In this review, we will discuss recent advances in RNA structure analysis techniques, including structural probing methods, X-ray crystallography, nuclear magnetic resonance, cryo-electron microscopy, and small-angle X-ray scattering. Often, a combination of multiple techniques is employed for the integrated analysis of RNA structures. We also survey important RNA structures that have been recently determined using various techniques.
PubMed: 38933295
DOI: 10.1016/j.fmre.2023.06.001 -
Frontiers in Immunology 2024B cell depleting anti-CD20 monoclonal antibodies (aCD20 mAbs) are highly effective in treatment of multiple sclerosis (MS) but fail to halt the formation of meningeal...
Single-cell profiling indicates a high similarity between immune cells in the cerebrospinal fluid and in meningeal ectopic lymphoid tissue in experimental autoimmune encephalomyelitis.
BACKGROUND AND OBJECTIVES
B cell depleting anti-CD20 monoclonal antibodies (aCD20 mAbs) are highly effective in treatment of multiple sclerosis (MS) but fail to halt the formation of meningeal ectopic lymphoid tissue (mELT) in the murine model experimental autoimmune encephalomyelitis (EAE). While mELT can be examined in EAE, it is not accessible in MS patients. Our key objectives were to compare the immune cells in cerebrospinal fluid (CSF), which is accessible in patients, with those in mELT, and to study the effects of aCD20 mAbs on CSF and mELT in EAE.
METHODS
Applying single cell RNA sequencing, we compared gene expression profiles in immune cells from (1) CSF with mELT and (2) aCD20 mAbs treated with control treated mice in a spontaneous 2D2xTh EAE model.
RESULTS
The immune cell composition in CSF and mELT was very similar. Gene expression profiles and pathway enrichment analysis revealed no striking differences between the two compartments. aCD20 mAbs led not only to a virtually complete depletion of B cells in the CSF but also to a reduction of naïve CD4+ T cells and marked increase of macrophages. No remarkable differences in regulated genes or pathways were observed.
DISCUSSION
Our results suggest that immune cells in the CSF may serve as a surrogate for mELT in EAE. Future studies are required to confirm this in MS patients. The observed increase of macrophages in B cell depleted CSF is a novel finding and requires verification in CSF of aCD20 mAbs treated MS patients. Due to unresolved technical challenges, we were unable to study the effects of aCD20 mAbs on mELT. This should be addressed in future studies.
Topics: Animals; Encephalomyelitis, Autoimmune, Experimental; Mice; Single-Cell Analysis; Meninges; B-Lymphocytes; Female; Tertiary Lymphoid Structures; Mice, Inbred C57BL; Antibodies, Monoclonal; Transcriptome; Gene Expression Profiling; Antigens, CD20; Cerebrospinal Fluid; Disease Models, Animal; Multiple Sclerosis
PubMed: 38933267
DOI: 10.3389/fimmu.2024.1400641 -
Fundamental Research May 2024Hybridization and polyploidization have made great contributions to speciation, heterosis, and agricultural production within plants, but there is still limited...
Hybridization and polyploidization have made great contributions to speciation, heterosis, and agricultural production within plants, but there is still limited understanding and utilization in animals. Subgenome structure and expression reorganization and cooperation post hybridization and polyploidization are essential for speciation and allopolyploid success. However, the mechanisms have not yet been comprehensively assessed in animals. Here, we produced a high-fidelity reference genome sequence for common carp, a typical allotetraploid fish species cultured worldwide. This genome enabled in-depth analysis of the evolution of subgenome architecture and expression responses. Most genes were expressed with subgenome biases, with a trend of transition from the expression of subgenome A during the early stages to that of subgenome B during the late stages of embryonic development. While subgenome A evolved more rapidly, subgenome B contributed to a greater level of expression during development and under stressful conditions. Stable dominant patterns for homoeologous gene pairs both during development and under thermal stress suggest a potential fixed heterosis in the allotetraploid genome. Preferentially expressing either copy of a homoeologous gene at higher levels to confer development and response to stress indicates the dominant effect of heterosis. The plasticity of subgenomes and their shifting of dominant expression during early development, and in response to stressful conditions, provide novel insights into the molecular basis of the successful speciation, evolution, and heterosis of the allotetraploid common carp.
PubMed: 38933191
DOI: 10.1016/j.fmre.2023.06.011 -
Journal of Molecular and Cellular... Jun 2024Heart failure remains one of the largest clinical burdens globally, with little to no improvement in the development of disease-eradicating therapeutics. Integrin...
Heart failure remains one of the largest clinical burdens globally, with little to no improvement in the development of disease-eradicating therapeutics. Integrin targeting has been used in the treatment of ocular disease and cancer, but little is known about its utility in the treatment of heart failure. Here we sought to determine whether the second generation orally available, αvβ3-specific RGD-mimetic, , was cardioprotective. Male mice were subjected to transverse aortic constriction (TAC) and treated with 50 μg/kg or volume-matched saline as Vehicle control. At 3 weeks post-TAC, echocardiography showed that treatment significantly restored cardiac function and structure indicating the protective effect of treatment in this model of heart failure. Importantly, treatment improved cardiac function giving improved fractional shortening, ejection fraction, heart weight and lung weight to tibia length fractions, together with partial restoration of Ace and Mme levels, as markers of the TAC insult. At a tissue level, reduced cardiomyocyte hypertrophy and interstitial fibrosis, both of which are major clinical features of heart failure. RNA sequencing identified that, mechanistically, this occurred with concomitant alterations to genes involved molecular pathways associated with these processes such as metabolism, hypertrophy and basement membrane formation. Overall, targeting αvβ3 with provides a novel strategy to attenuate pressure-overload induced cardiac hypertrophy and fibrosis, providing a possible new approach to heart failure treatment.
PubMed: 38933087
DOI: 10.1016/j.jmccpl.2024.100069 -
Frontiers in Microbiology 2024Demand for natural gas continues to climb in the United States, having reached a record monthly high of 104.9 billion cubic feet per day (Bcf/d) in November 2023....
Demand for natural gas continues to climb in the United States, having reached a record monthly high of 104.9 billion cubic feet per day (Bcf/d) in November 2023. Hydraulic fracturing, a technique used to extract natural gas and oil from deep underground reservoirs, involves injecting large volumes of fluid, proppant, and chemical additives into shale units. This is followed by a "shut-in" period, during which the fracture fluid remains pressurized in the well for several weeks. The microbial processes that occur within the reservoir during this shut-in period are not well understood; yet, these reactions may significantly impact the structural integrity and overall recovery of oil and gas from the well. To shed light on this critical phase, we conducted an analysis of both pre-shut-in material alongside production fluid collected throughout the initial production phase at the Hydraulic Fracturing Test Site 2 (HFTS 2) located in the prolific Wolfcamp formation within the Permian Delaware Basin of west Texas, USA. Specifically, we aimed to assess the microbial ecology and functional potential of the microbial community during this crucial time frame. Prior analysis of 16S rRNA sequencing data through the first 35 days of production revealed a strong selection for a species corresponding to a significant decrease in microbial diversity. Here, we performed a metagenomic analysis of produced water sampled on Day 33 of production. This analysis yielded three high-quality metagenome-assembled genomes (MAGs), one of which was a draft genome closely related to the recently classified . This draft genome likely represents the dominant species observed in our 16S rRNA profile. Annotation of the MAGs revealed the presence of genes involved in critical metabolic processes, including thiosulfate reduction, mixed acid fermentation, and biofilm formation. These findings suggest that this microbial community has the potential to contribute to well souring, biocorrosion, and biofouling within the reservoir. Our research provides unique insights into the early stages of production in one of the most prolific unconventional plays in the United States, with important implications for well management and energy recovery.
PubMed: 38933028
DOI: 10.3389/fmicb.2024.1376536 -
Frontiers in Microbiology 2024Commensal microbial-host interaction is crucial for host metabolism, growth, development, and immunity. However, research on microbial-host immunity in large animal...
Commensal microbial-host interaction is crucial for host metabolism, growth, development, and immunity. However, research on microbial-host immunity in large animal models has been limited. This study was conducted to investigate the effects of the commensal microbiota on immune function in two model groups: germ-free (GF) and specific-pathogen-free (SPF) piglets. The weight and organ index of the spleen of the GF piglet were larger than those in the SPF piglet ( < 0.05). The histological structure of the red pulp area and mean area of germinal centers were larger in the SPF piglet than in the GF piglet ( < 0.05), whereas the areas of staining of B cells and T cells in the spleen and mesenteric lymph nodes (MLNs) were lower in the GF piglet ( < 0.05). We identified immune-related genes in the spleen and MLNs using RNA sequencing, and used real-time quantitative PCR to analyze the expression of core genes identified in gene set enrichment analysis. The expression levels of genes in the transforming growth factor-β/SMAD3 signaling pathway, Toll-like receptor 2/MyD88/nuclear factor-κB signaling pathway, and pro-inflammatory factor genes and in the spleen and MLNs were higher in the SPF piglet and in splenic lymphocytes compared with those in the GF and control group, respectively, under treatment with acetic acid, propionic acid, butyric acid, lipopolysaccharide (LPS), or concanavalin A (ConA). The abundances of plasma cells, CD8 T cells, follicular helper T cells, and resting natural killer cells in the spleen and MLNs were significantly greater in the SPF piglet than in the GF piglet ( < 0.05). In conclusion, the commensal microbiota influenced the immune tissue structure, abundances of immune cells, and expression of immune-related pathways, indicating the importance of the commensal microbiota for spleen and MLNs development and function. In our study, GF piglet was used as the research model, eliminating the interference of microbiota in the experiment, and providing a suitable and efficient large animal research model for exploring the mechanism of "microbial-host" interactions.
PubMed: 38933022
DOI: 10.3389/fmicb.2024.1398631 -
Frontiers in Microbiology 2024Deltacoronavirus, widely distributed among pigs and wild birds, pose a significant risk of cross-species transmission, including potential human epidemics. Metagenomic...
Deltacoronavirus, widely distributed among pigs and wild birds, pose a significant risk of cross-species transmission, including potential human epidemics. Metagenomic analysis of bird samples from Qinghai Lake, China in 2021 reported the presence of Deltacoronavirus. A specific gene fragment of Deltacoronavirus was detected in fecal samples from wild birds at a positive rate of 5.94% (6/101). Next-generation sequencing (NGS) identified a novel Deltacoronavirus strain, which was closely related to isolates from the United Arab Emirates (2018), China (2022), and Poland (2023). Subsequently the strain was named A/black-headed gull/Qinghai/2021(BHG-QH-2021) upon confirmation of the Cytochrome b gene of black-headed gull in the sample. All available genome sequences of avian Deltacoronavirus, including the newly identified BHG-QH-2021 and 5 representative strains of porcine Deltacoronavirus (PDCoV), were classified according to ICTV criteria. In contrast to , which infects both mammals and birds and shows the possibility of cross-species transmission from bird to mammal host, our analysis revealed that BHG-QH-2021 is classified as . has been reported to infect 5 species of birds but not mammals, suggesting that cross-species transmission of is more prevalent among birds. Recombination analysis traced BHG-QH-2021 origin to dut148cor1 and MW01_1o strains, with MW01_1o contributing the S gene. Surprisingly, SwissModle prediction showed that the optimal template for receptor-binding domain (RBD) of BHG-QH-2021 is derived from the human coronavirus 229E, a member of the Alphacoronavirus, rather than the anticipated RBD structure of PDCoV of Deltacoronavirus. Further molecular docking analysis revealed that substituting the loop 1-2 segments of HCoV-229E significantly enhanced the binding capability of BHG-QH-2021 with human Aminopeptidase N (hAPN), surpassing its native receptor-binding domain (RBD). Most importantly, this finding was further confirmed by co-immunoprecipitation experiment that loop 1-2 segments of HCoV-229E enable BHG-QH-2021 RBD binding to hAPN, indicating that the loop 1-2 segment of the RBD in is a probable key determinant for the virus ability to spill over into humans. Our results summarize the phylogenetic relationships among known Deltacoronavirus, reveal an independent putative avian Deltacoronavirus species with inter-continental and inter-species transmission potential, and underscore the importance of continuous surveillance of wildlife Deltacoronavirus.
PubMed: 38933020
DOI: 10.3389/fmicb.2024.1423367 -
Ecology and Evolution Jun 2024(cav.) Weatherby, commonly known as mountain stewartia, is an understory tree native to the southeastern United States (U.S.). This relatively rare species occurs in...
(cav.) Weatherby, commonly known as mountain stewartia, is an understory tree native to the southeastern United States (U.S.). This relatively rare species occurs in isolated populations in Virginia, Kentucky, Tennessee, North Carolina, South Carolina, Georgia, Alabama, and Mississippi. As a species, has largely been overlooked, and limited information is available regarding its ecology, which presents obstacles to conservation efforts. has vibrant, large white flowers that bloom in summer with a variety of filament colors, suggesting potential horticultural traits prized by ornamental industry. However, is relatively slow growing and, due to long seed dormancy, propagation is challenging with limited success rates. This has created a need to assess the present genetic diversity in populations to inform potential conservation and restoration of the species. Here, we employ a genotyping-by-sequencing (GBS) approach to characterize the spatial distribution and genetic diversity of in the southern Appalachia region of the eastern United States. A total of 4475 single nucleotide polymorphisms (SNPs) were identified across 147 individuals from 11 collection sites. Our results indicate low genetic diversity (He = 0.216), the presence of population structure ( = 2), limited differentiation ( = 0.039), and high gene flow (Nm = 6.16) between our subpopulations. Principal component analysis corroborated the findings of STRUCTURE, confirming the presence of two distinct subpopulations. One subpopulation mainly contains genotypes from the Cumberland Plateau, Tennessee, while the other consists of genotypes present in the Great Smoky Mountain ranges in Tennessee, North Carolina, and portions of Nantahala, Chattahoochee-Oconee national forests in Georgia, highlighting that elevation likely plays a major role in its distribution. Our results further suggested low inbreeding coefficient ( = 0.070), which is expected with an outcrossing tree species. This research further provides necessary insight into extant subpopulations and has generated valuable resources needed for conservation efforts of .
PubMed: 38932967
DOI: 10.1002/ece3.11547