Search bioRxiv⌕ Search

Biology subjects

Chao, S.

Publications and source records attributed to Chao, S..

9 recordsLinked to original sources

Physiological Aging and Cardiovascular Disease Distinctly Remodel the Human Cardiac Lymphatic Endothelium

Aims: Cardiac lymphatic endothelial cells (LECs) regulate tissue homeostasis, immune trafficking, and remodeling, but how human cardiac LEC heterogeneity changes with physiological aging and cardiovascular disease remains poorly defined. We sought to define age- and disease-associated LEC states, their regulatory and microenvironmental programs, and the functional relevance of selected pathways. Methods and results: We integrated human cardiac single-nucleus transcriptomic datasets spanning physiological aging, dilated and hypertrophic cardiomyopathy, doxorubicin-associated cardiomyopathy, and heart failure with preserved ejection fraction. Aging redistributed LECs among pre-existing states, with expansion of a homeostatic immune-surveillance state and loss of cytokine-responsive and polarity-associated states. Cardiovascular diseases showed a distinct trajectory, with depletion of a non-failing homeostatic state and expansion of shared and disease-associated remodeling states. SCENIC and NicheNet/MultiNicheNet identified state-specific regulatory programs and disease-dependent signaling networks, with recurrent BMP/TGF-{beta}/activin-family signaling. ACVR2A was prioritized in human doxorubicin-associated cardiomyopathy; endothelial Acvr2a deletion in aged doxorubicin-treated mice was associated with improved cardiac function and increased open cardiac lymphatic vessels. Independent human spatial transcriptomic analyses supported selected aging- and disease-associated programs. Conclusion: Physiological aging and cardiovascular disease remodel cardiac LECs through distinct changes in cellular state, transcriptional regulation, and microenvironmental signaling. Aging is associated with redistribution and reduced representation of specialized LEC programs, whereas cardiovascular diseases redirect LECs through disease-associated signaling environments, highlighting context-dependent remodeling of the cardiac lymphatic endothelium across aging and disease.

bioinformatics↗

Insights into the Biocontrol Mechanisms of a Paenibacilluspeoriae Strain on Maize Seedling Blight through Multi-Omics Analysis

Maize seedling blight, caused by the phytopathogenic fungus Fusarium verticillioides, is a common and rapidly spreading disease that negatively impacts grain quality and productivity. Control of this pathogen is complicated by its complex infection process and the tendency for resistance to conventional chemical pesticides. The use of biological control agents has been recognized as an environmentally friendly and sustainable solution for the control of plant diseases. In our study, we isolated and identified Paenibacillus peoriae 3-B4 from maize leaves, which exhibited an inhibition rate of 59.92% against F. verticillioides in greenhouse experiments. Genome sequencing of P. peoriae 3-B4 revealed a chromosome of 5,912,131 bp, featuring a GC content of 45.51% on average and 5383 annotated coding sequences. Eight gene clusters associated with secondary metabolites with antifungal activity and thirteen genes associated with induced systemic resistance and pattern-triggered immunity were identified. Transcriptomic analysis identified 8,997 differentially expressed maize genes, with key defense genes (e.g., NPR1, bZIP, MYB, LRR, WRKY) enriched in MAPK signaling and plant-pathogen interactions. 16S rRNA analysis showed significant shifts in microbial communities, particularly with an increase in the abundance of beneficial genera like Paenibacillus, Delftia, and Corynebacterium. The combined analysis of differentially expressed genes and microbial communities indicated that they synergistically enhance pathogen resistance in maize. Our findings outline the potential mechanisms by which P. peoriae 3-B4 inhibits F. verticillioides infection and open possibilities of exploiting biological control strategies to control maize seedling blight.

microbiology↗

Network pharmacological evaluation of active ingredients and potential targets of San Huang Decoction in the treatment of breast cancer

ObjectiveUsing the method of network pharmacology, the possible targets and related signaling pathways of San Huang Decoction against breast cancer were explored. MethodsThe active ingredients of San Huang Decoction were screened in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). All targets of San Huang Decoction and breast cancer were obtained through five databases, and R software was used to obtain their common targets. Then, Cytoscape software was used to construct the active ingredient-target network map. The protein-protein interaction network (PPI) was obtained with the help of the STRING database, and key targets were screened out through network topology analysis. Common targets were subjected to gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis using R software. ResultsA total of 39 active ingredients were screened from San Huang Decoction, of which 20 belonged to Huangqi, 16 belonged to Dahuang, and 3 belonged to Jianghuang. After taking the intersection of all the targets of San Huang Decoction and breast cancer, a total of 185 potential targets of San Huang Decoction against breast cancer were obtained. PPI network analysis screened out 16 targets that may be the key targets of San Huang Decoction against breast cancer. The enrichment analysis of GO and KEGG suggested that the common targets were involved in various biological processes and functions through PI3K-Akt signaling pathway, MAPK signaling pathway, TNF signaling pathway, IL-17 signaling pathway, and HIF-1 signaling pathway, including oxidation stress, transcription-related functions, and nuclear receptor functions. ConclusionThis study predicted the potential targets and signaling pathways of San Huang Decoction against breast cancer, and provided scientific guidance for the further study on the anti-breast cancer mechanism of San Huang Decoction.

bioinformatics↗

Maternal obesity may disrupt offspring metabolism by inducing oocyte genome hyper-methylation via increased DNMTs

Maternal obesity has deleterious effects on the process of establishing oocyte DNA methylation; yet the underlying mechanisms remain unclear. In the present study, we found that maternal obesity induced by high-fat diet (HFD) disrupted the genomic methylation of oocytes, and that at least a part of the altered DNA methylation was transmitted to the F2 oocytes and the livers via females. We further examined the metabolome of serum and found that the altered metabolites such as melatonin may play a key role in the disrupted genomic methylation in the oocytes of obese mice. We further found that exogenous melatonin treatment significantly reduced the hyper-methylation of HFD oocytes, and the increased expression of DNMT3a and DNMT1 in HFD oocytes was also decreased. To address how melatonin regulates the expression of DNMTs, the function of melatonin was inhibited or activated upon oocytes. Results revealed that melatonin may regulate the expression of DNMTs via the cAMP/PKA/CREB pathway. These results suggest that maternal obesity induces genomic methylation alterations in oocytes, which can be partly transmitted to F2 in females, and that melatonin is involved in regulating the hyper-methylation of HFD oocytes by increasing the expression of DNMTs via the cAMP/PKA/CREB pathway.

developmental biology↗

The genomic landscape of swine influenza A viruses in Southeast Asia

Swine are a primary source for the emergence of pandemic influenza A viruses. The intensification of swine production, along with global trade, has amplified the transmission and zoonotic risk of swine influenza virus (swIAV). Effective surveillance is essential to uncover emerging virus strains, however gaps remain in our understanding of the swIAV genomic landscape in Southeast Asia. By collecting more than 4,000 nasal swabs and 4,000 sera from pigs in Cambodia, we unmasked the co-circulation of multiple lineages of genetically diverse swIAV of pandemic concern. Genomic analyses revealed a novel European avian-like H1N2 swine reassortant variant with North American triple reassortant internal genes, that emerged approximately seven years before its first detection in pigs in 2021. Using phylogeographic reconstruction, we identified south central China as the dominant source of swine viruses disseminated to other regions in China and Southeast Asia. We also identified nine distinct swIAV lineages in Cambodia, which diverged from their closest ancestors between two to 15 years ago, indicating significant undetected diversity in the region, including reverse zoonoses of human H1N1/2009 pandemic and H3N2 viruses. A similar period of cryptic circulation of swIAVs occurred in the decades before the H1N1/2009 pandemic. The hidden diversity of swIAV observed here further emphasizes the complex underlying evolutionary processes present in this region, reinforcing the importance of genomic surveillance at the human-swine interface for early warning of disease emergence to avoid future pandemics.

microbiology↗

Nuclear progesterone receptor regulates blood coagulation facilitating ovulation in zebrafish

Ovulation is a dramatic remodeling process that includes rupture of blood capillaries and clotting, but coagulation is not thought to directly regulate this process. Herein, we report remarkable increases of coagulation factors V (f5, [~]3145-fold) and tissue factor (f3a, [~]120-fold) in zebrafish ovarian follicle cells during ovulation. This increase was mediated through the nuclear progestin receptor (Pgr), which is essential for ovulation in zebrafish, and was totally abolished in ovarian follicular cells from pgr-/- mutants. In addition, promoter activities of f5 and f3a were significantly enhanced by progestin (DHP) via Pgr. Similar regulation of human F5 promoter activity was induced via human PGRB, suggesting a conserved mechanism. Site-directed mutagenesis of the zebrafish f5 promoter further demonstrated a direct regulation of coagulation factors via progestin response elements. Moreover, a stark increase of erythrocytes occurred in capillaries meshed in wildtype preovulatory follicles but was absent in pgr-/- mutants. Interestingly, anticoagulants significantly inhibited ovulation both in vitro and in vivo, respectively. Furthermore, reduced fecundity was observed in f5+/- female zebrafish. Taken together, our study provides plausible evidence for steroid regulation of coagulation factors, and a new hypothesis for blood clotting triggered ovulation in vertebrates.

physiology↗

Natural genetic variation underlying tiller development in barley (Hordeum vulgare L)

In barley (Hordeum vulgare L.), lateral branches called tillers contribute to grain yield and define shoot architecture, but genetic control of tiller number and developmental rate are not well characterized. The primary objectives of this work were to examine relationships between tiller number and other agronomic and morphological traits and identify natural genetic variation associated with tiller number and rate, and related traits. We grew 768 lines from the USDA National Small Grain Core Collection in the field and collected data over two years for tiller number and rate, and agronomic and morphological traits. Our results confirmed that spike row-type and days to heading are correlated with tiller number, and as much as 28% of tiller number variance is attributed to these traits. In addition, negative correlations between tiller number and leaf width and stem diameter were observed, indicating trade-offs between tiller development and other vegetative growth. Thirty-three quantitative trait loci (QTL) were associated with tiller number or rate. Of these, 40% overlapped QTL associated with days to heading and 22% overlapped QTL associated with spike row-type, further supporting that tiller development is influenced by these traits. Despite this, some QTL associated with tiller number or rate, including the major QTL on chromosome 3H, were not associated with any other traits, suggesting that tiller number can be modified independently of other important agronomic traits. These results enhance our knowledge of the genetic control of tiller development in barley, which is important for optimizing tiller number and rate for yield improvement.

genetics↗

Potassium nutrition recover impacts on stomatal, mesophyll and biochemical limitations to photosynthesis in Carya cathayensis and Hickory illinoensis

Potassium (K) influences the photosynthesis process in a number of ways; However, the mechanism of photosynthetic response to the long-term supply of potassium is not yet clear. Concurrent measurements of gas exchange and chlorophyll fluorescence were made to investigate the effect of potassium nutrition on photosynthetic efficiency and stomatal conductance (gs), mesophyll conductance (gm) in Pecan (Carya illinoensis K.Kock) and Hickory (Carya cathayensis Sarg.) seedlings in a greenhouse. The results show that the photosynthetic capacity of Pecan and Hickory plants was not limited when the leaves had potassium concentrations >1.4% and 1.42% of dry weight. Most of limitation under potassium deficiency were dominated by MCL for Pecan and Hickory. Both cultivars showed remarkable improvement in SL, MCL, J and Vc,max with additional K supplies. However, effect from potassium deficiency on photosynthesis in plant leaves was irreversible. All of SL, MCL, and BL nearly half down with recovery K supply in both species. These results emphasize the important role of potassium on regulation of photosynthesis by three limitations.

physiology↗

Genome-wide homology analysis reveals new insights into the origin of the wheat B genome

Wheat is a typical allopolyploid with three homoeologous subgenomes (A, B, and D). The ancestors of the subgenomes A and D had been identified, but not for the subgenome B. The goatgrass Aegilops speltoides (genome SS) has been controversially considered a candidate for the ancestor of the wheat B genome. However, the relationship of the Ae. speltoides S genome with the wheat B genome remains largely obscure, which has puzzled the wheat research community for nearly a century. In the present study, the genome-wide homology analysis identified perceptible homology between wheat chromosome 1B and Ae. speltoides chromosome 1S, but not between other chromosomes in the B and S genomes. An Ae. speltoides-originated segment spanning a genomic region of approximately 10.46 Mb was identified on the long arm of wheat chromosome 1B (1BL). The Ae. speltoides-originated segment on 1BL was found to co-evolve with the rest of the B genome in wheat species. Thereby, we conclude that Ae. speltoides had been involved in the origin of the wheat B genome, but should not be considered an exclusive ancestor of this genome. The wheat B genome might have a polyphyletic origin with multiple ancestors involved, including Ae. speltoides. These novel findings provide significant insights into the origin and evolution of the wheat B genome, and will facilitate polyploid genome studies in wheat and other plants as well.

genetics↗