Biology subjects

Mo, H.

Publications and source records attributed to Mo, H..

12 recordsLinked to original sources

bioRxiv2026

Population Structure and Antimicrobial Resistance Gene Transfer of Respiratory Escherichia coli Isolated from Swine in China

ABSTRACPorcine respiratory diseases caused by extraintestinal pathogenic Escherichia coli (ExPEC) pose a severe threat to swine production and public health; however, research on respiratory tract-isolated ExPEC remains limited. This study comprehensively analyzed the genomic characteristics and antibiotic resistance gene (ARG) transfer potential of 441 ExPEC strains isolated from porcine lungs across 21 Chinese provinces (including 53 newly isolated strains from 2022-2024 and 388 NCBI-deposited strains). Phylogenetic analysis revealed that 84% of the isolates belonged to phylogroups A, B1, and C, with ST410, ST101, and ST88 as the predominant STs. The strains exhibited extensive ARG diversity, harboring 111 distinct ARG subtypes, with sul2 (81.4%), floR (73.5%), and tet (A) (68.0%) being the most prevalent. Importantly, critical "last-resort" antibiotic resistance genes (e.g., blaNDM-1/5, the mcr family, and tet (X4)) were also detected. Notably, 77.2% of the ARGs presented horizontal transfer potential, with plasmids (especially IncF family replicons) serving as core vectors, followed by integrons and transposons. Cooccurrence network analysis identified aph (3)-Ib, aph (6)-Id, sul2, and floR as core subnetworks driving multidrug resistance dissemination. Pangenomic analysis confirmed an open genome architecture, with core genes accounting for only 6%, reflecting the strains capacity to acquire exogenous genetic material via horizontal transfer. From the One Health perspective, these transferable ARGs can spread to the environment and humans through fecal discharge and the food chain. These findings underscore the importance of monitoring and controlling ExPEC infections in swine, as such strains can as reservoirs of ARGs, pose potential risks to human health, and may even act as sources of pathogenic agents responsible for human infections. IMPORTANCEPorcine respiratory ExPEC-induced diseases threaten swine production and public health, yet respiratory tract-isolated ExPEC research remains scarce. This study comprehensively analyzed 441 porcine lung ExPEC strains across 21 Chinese provinces, uncovering their dominant phylogroups, high ARG diversity (111 subtypes) and the presence of "last-resort" antibiotic resistance genes. We identified 77.2% of ARGs with horizontal transfer potential, plasmids (especially IncF family) as core vectors, and a core ARG subnetwork driving multidrug resistance. The open pangenome (6% core genes) highlights ExPECs strong capacity to acquire exogenous genes. These findings fill the research gap of respiratory ExPEC, clarify ARG transmission mechanisms in swine ExPEC, and provide critical genomic data for One Health-based AMR surveillance and control, guiding targeted strategies to mitigate ARG spread from swine to humans and the environment.

microbiology↗

bioRxiv2025

Oral dosing of the nucleoside analog obeldesivir is efficacious against RSV infection in African green monkeys

Respiratory syncytial virus (RSV) is a significant cause of morbidity and mortality in high-risk populations. Although prophylactic options are available, there are no effective oral therapeutics for RSV infection. Obeldesivir (ODV) is an orally bioavailable prodrug of the nucleoside analog GS-441524, which is converted intracellularly to its active nucleoside triphosphate and inhibits the RSV RNA polymerase. Here we report the potent antiviral activity of ODV against geographically and temporally diverse RSV A and B clinical isolates (EC50: 0.20-0.66 M). Resistance selection studies with ODV and GS-441524 against RSV identified a single amino acid substitution, I777L, in the L polymerase with reduced susceptibility (3.3-3.8-fold) to ODV and GS-441524, indicating a high barrier for resistance development. In an African green monkey RSV infection model, once-daily oral ODV doses of 30 or 90 mg/kg initiated [~]24 hours post-infection significantly reduced log10 viral RNA copies/mLxday area under the curve by 69-92% in the upper and lower respiratory tracts. Together, these preclinical data support the clinical evaluation of ODV for the treatment of RSV infection.

microbiology↗

bioRxiv2024

Mechano-regulation of GLP-1 production by Piezo1 in intestinal L cells

Glucagon-like peptide 1 (GLP-1) is a gut-derived hormone secreted by intestinal L cells and vital for postprandial glycemic control. As open-type enteroendocrine cells, whether L cells can sense mechanical stimuli caused by chyme and thus regulate GLP-1 synthesis and secretion is unexplored. Our study showed expression of Piezo1 in intestinal L cells. Its level varied in different energy status and correlates with blood glucose and GLP-1 levels. Mice with L cell-specific loss of Piezo1 (IntL-Piezo1-/-) exhibited impaired glucose tolerance, increased body weight, reduced GLP-1 production and decreased CaMKK{beta}/CaMKIV-mTORC1 signaling pathway under normal chow diet or high fed diet. Activation of the intestinal Piezo1 by its agonist Yoda1 or intestinal bead implantation increased the synthesis and secretion of GLP-1, thus alleviated glucose intolerance in diet-induced-diabetic mice. Overexpression of Piezo1, Yoda1 treatment or stretching stimulated GLP-1 production and CaMKK{beta}/CaMKIV-mTORC1 signaling pathway, which could be abolished by knockdown or blockage of Piezo1 in primary cultured mouse L cells and STC-1 cells. These findings suggest a previously undiscovered mechano-regulation of GLP-1 production in L cells, which may shed new light on the treatments of diabetes.

physiology↗

bioRxiv2023

Tumors cells with mismatch repair deficiency induce hyperactivation of Pyroptosis resistant to cell membrane damage but are more sensitive to Co-treatment of IFN-γ and TNF-α to PANoptosis

Hypermutated neoantigens in cancers with DNA mismatch repair deficiency (dMMR) are prerequisite for favorable clinical responses to immune-checkpoint blockade (ICB) therapy. However, TMB is not significantly associated with favorable prognosis from Preclinical and clinical studies. It implys that except for TMB, other mechanisms should be needed to contribute to successful cancer immunotherapy. We found that the hyperactivation of PANoptotic effective molecules in dMMR tumor cells caused cell membrane damage, and induced ESCRT mediated membrane repair, and protectd tumor cells from the damage caused by Triton X100, while DNA mismatch repair proficient (pMMR) tumor cells were sensitive to Triton X100 mediating cell membrane damage due to the lack of ESCRT mediated membrane repair. There were hyperactivation of GSDMD, GSDME and p-MLKL in dMMR tumor cells. Co-treatment of IFN-{gamma} and TNF- induced rapid death of dMMR tumor cells by inducing PANoptosis including pyroptosis, apoptosis not necrosis. pMMR tumor cells had defects in PANoptosis pathway and were resistant to co-treatment of IFN-{gamma} and TNF-. In conclusion, we can activate immune cells to release IFN-{gamma} and TNF- to overcome resistance to ICB treatment.

cancer biology↗

bioRxiv2022

Transgene by Germplasm Interactions Can Impact Transgene Evaluation

Transgenes have been successfully commercialized for qualitatively inherited insect and herbicide resistance traits that show similar effects across genetic backgrounds. However, for quantitative traits like yield, genetic background may affect the measured transgene value. In this paper, we evaluated whether different genetic backgrounds impact the estimated value of a transgene for grain yield, ear height, and anthesis-silking interval for maize by developing isogenic pairs of lines with and without a transgene and testing them in hybrid combination with non-transgenic lines from a complementary heterotic group across eleven environments in the USA. Over all hybrid combinations, the transgene increased yield by 0.2 Mg ha-1. Across multiple non-transgenic lines of the opposing heterotic group, the transgene effect within a line pair ranged from an increase of 0.8 Mg ha-1 for the NSS4 and SS7 transgenic lines to a reduction of 0.3 Mg ha-1 for the NSS5 transgenic line when compared to their non-transgenic isoline. Transgenic hybrids were often taller than non-transgenic hybrids (P<0.05). Anthesis to silking interval was reduced by 4{square}C growing degree units overall, but no transgene x genotype interaction was detected among line pairs. Our results show the importance of testing transgene efficacy across a large sample of elite hybrid pairs to assess the genes value. By only testing in a specific hybrid background, as may be done for qualitative traits like insect resistance, transgenes could be erroneously advanced or eliminated.

plant biology↗

bioRxiv2022

Methods for Evaluating Effects of Transgenes for Quantitative Traits

Transgenes that improve quantitative traits have traditionally been evaluated in one or a few genetic backgrounds across multiple environments. However, testing across multiple genetic backgrounds can be equally important to accurately quantify the value of a transgene for breeding objectives. Creating near-isogenic lines across a wide germplasm space is costly and time consuming, which renders it impractical during early stages of testing. In this experiment, we evaluate three approaches to sample the genetic space while concurrently testing across environments. We created both transgenic and non-transgenic doubled haploid lines, F2:3 lines, and bulk F3 families to determine if all methods resulted in similar estimation of transgene value and to identify the number of yield trial plots from each method necessary to obtain a stable estimate of the transgene value. With one exception, the three methods consistently estimated a similar effect of the transgene. We suggest that bulked F3 lines topcrossed to a tester inbred is the most effective method to estimate the value of a transgene across both genetic space and environments.

plant biology↗

bioRxiv2022

Remdesivir and GS-441524 retain antiviral activity against Delta, Omicron, and other emergent SARS-CoV-2 variants

Genetic variation of SARS-CoV-2 has resulted in the emergence and rapid spread of multiple variants throughout the pandemic, of which Omicron is currently the predominant variant circulating worldwide. SARS-CoV-2 variants of concern or interest (VOC/VOI) have evidence of increased viral transmission, disease severity, or decreased effectiveness of vaccines and neutralizing antibodies. Remdesivir (RDV, VEKLURY(R)) is a nucleoside analog prodrug and the first FDA-approved antiviral treatment of COVID-19. Here we present a comprehensive antiviral activity assessment of RDV and its parent nucleoside, GS-441524, against 10 current and former SARS-CoV-2 VOC/VOI clinical isolates by nucleoprotein ELISA and plaque reduction assay. Delta and Omicron variants remained susceptible to RDV and GS-441524, with EC50 values 0.31 to 0.62-fold of those observed against the ancestral WA1 isolate. All other tested variants exhibited EC50 values ranging from 0.15 to 2.3-fold of the observed EC50 values against WA1. Analysis of nearly 6 million publicly available variant isolate sequences confirmed that Nsp12, the RNA-dependent RNA polymerase (RdRp) target of RDV and GS-441524, is highly conserved across variants with only 2 prevalent changes (P323L and G671S). Using recombinant viruses, both RDV and GS-441524 retained potency against all viruses containing frequent variant substitutions or their combination. Taken together, these results highlight the conserved nature of SARS-CoV-2 Nsp12 and provide evidence of sustained SARS-CoV-2 antiviral activity of RDV and GS-441524 across the tested variants. The observed pan-variant activity of RDV supports its continued use for the treatment of COVID-19 regardless of the SARS-CoV-2 variant.

microbiology↗

bioRxiv2021

Spatially Resolved Phosphoproteomics Reveals Fibroblast Growth Factor Receptor Recycling-driven Regulation of Autophagy and Survival

Receptor Tyrosine Kinase (RTK) endocytosis-dependent signalling drives cell proliferation and motility during development and adult homeostasis, but is dysregulated in diseases, including cancer. The recruitment of RTK signalling partners during endocytosis, specifically during recycling to the plasma membrane, is still unknown. Focusing on Fibroblast Growth Factor Receptor 2b (FGFR2b) recycling, we revealed FGFR signalling partners proximal to recycling endosomes (REs) by developing a Spatially Resolved Phosphoproteomics (SRP) approach based on APEX2-driven biotinylation followed by phosphopeptide enrichment. Combining this with traditional phosphoproteomics, bioinformatics, and targeted assays, we uncovered that FGFR2b stimulated by its recycling ligand FGF10 activates mTOR-dependent signalling and ULK1 at the REs, leading to autophagy suppression and cell survival. This adds to the growing importance of RTK recycling in orchestrating cell fate and suggests a therapeutically targetable vulnerability in ligand-responsive cancer cells. Integrating SRP with other systems biology approaches provides a powerful tool to spatially resolve celllar signalling.

cell biology↗

bioRxiv2021

The gut microbial signature of gestational diabetes mellitus and the association with diet intervention

Gestational diabetes mellitus (GDM) is a high-risk pregnancy complication that is associated with metabolic disorder phenotypes, such as abnormal blood glucose and obesity. The link between microbiota and diet management contributes to metabolic homeostasis in GDM. Therefore, it is crucial to understand the structure of the gut microbiota in GDM and to explore the effect of dietary management on the microbiota structure. In this study, we analyzed the composition of the gut microbiota between 27 GDM and 30 healthy subjects at two time points using Illumina HiSeq 2500 platform. The taxonomy analyses suggested that the overall bacteria clustered by diabetes status, rather than diet intervention. Of particular interest, the phylum Acidobacteria in GDM was significantly increased, and positively correlated with blood glucose levels. Moreover, Partial least-squares discriminant analysis (PLS-DA) revealed that certain genera in the phyla Firmicutes, Bacteroidetes, Proteobacteria, and Lentisphaerae characterized the GDM gut microbiota. Correlation analysis indicated that blood glucose levels and BMI index were correlated with the relative abundance of SCFAS-producing genera. Through the comparison between the GDM and healthy samples with or without diet intervention, we discovered that the role of short-term diet management in GDM processes is associated with the change in the Firmicutes/Bacteroidetes ratio and some specific taxa, rather than an alternative gut microbial pattern. Our study have important implications for understanding the beneficial effects of diet intervention on the specific gut microbiota and thus possibly their metabolism in pregnant women with GDM. ImportanceUnderstanding the composition and dynamics of the gut microbiota in GDM women under diet intervention is important because there may be opportunities for preventive strategies. We examined the relationships between GDM gut microbiota at two times before and after the diet intervention during second trimester of pregnancy and clinical characteristics in cohort of GDM women. We found that short-term diet management in GDM processes is associated with changes in the Firmicutes/Bacteroidetes ratio and some specific taxa rather than an alternative gut microbial pattern. Our study highlights the importance of considering diet intervention as the rescue of microbial dysfunction of GDM disease and can serve as a strategy for early prevention in future study.

microbiology↗

bioRxiv2020

Genome Wide Characterization, Identification And Expression Analysis Of Erf Gene Family In Cotton

ERF is a subfamily of AP2/EREBP superfamily, contained single AP2 domain. The overexpression of ERF genes steered to abiotic stress tolerance and pathogen resistance in transgenic plants. Here, a genome-wide analysis of ERF gene family within two diploid species (G. arboreum & G. raimondii) and two tetraploid species (G. barbadense, G. hirsutum) was performed. A total of 118, 120, 213, 220 genes contained sequence single AP2 domain were identified in G. arboreum, G. raimondii, G. barbadense and G. hirsutum respectively. The identified genes were unevenly distributed across 13/26 chromosomes of A and D genomes of cotton. Genome comparison revealed that segmental duplication may have played crucial roles in the expansion of the cotton ERF gene family, and tandem duplication also played a minor role. Analysis of RNA-Seq data indicated that cotton ERF gene expression levels varied across different tissues and in response to different abiotic stress. Overall, our results could provide valuable information for better understanding the evolution of cotton ERF genes and lays a foundation for future investigation in cotton.

bioinformatics↗

bioRxiv2020

Genetic Conservation of SARS-CoV-2 RNA Replication Complex in Globally Circulating Isolates from Humans and Minks Predicts Minimal Pre-Existing Resistance to Remdesivir

Remdesivir (RDV) exhibits potent antiviral activity against SARS-CoV-2 and is currently the only drug approved for the treatment of COVID-19. However, little is currently known about the potential for pre-existing resistance to RDV and the possibility of SARS-CoV-2 genetic diversification that might impact RDV efficacy as the virus continue to spread globally. In this study, >90,000 SARS-CoV-2 sequences from globally circulating clinical isolates, including sequences from recently emerged United Kingdom and South Africa variants, and >300 from mink isolates were analyzed for genetic diversity in the RNA replication complex (nsp7, nsp8, nsp10, nsp12, nsp13, and nsp14) with a focus on the RNA-dependent RNA polymerase (nsp12), the molecular target of RDV. Overall, low genetic variation was observed with only 12 amino acid substitutions present in the entire RNA replication complex in [≥]0.5% of analyzed sequences with the highest overall frequency (82.2%) observed for nsp12 P323L that consistently increased over time. Low sequence variation in the RNA replication complex was also observed among the mink isolates. Importantly, the coronavirus Nsp12 mutations previously selected in vitro in the presence of RDV were identified in only 2 isolates (0.002%) within all the analyzed sequences. In addition, among the sequence variants observed in [≥]0.5% clinical isolates, including P323L, none were located near the established polymerase active site or sites critical for the RDV mechanism of inhibition. In summary, the low diversity and high genetic stability of the RNA replication complex observed over time and in the recently emerged SARS-CoV-2 variants suggests a minimal global risk of pre-existing SARS-CoV-2 resistance to RDV.

genomics↗

bioRxiv2018

Pervasive adaptation of hepatitis C virus to interferon lambda polymorphism across multiple genotypes

Genetic polymorphism in the interferon lambda (IFN-{lambda}) region is associated with spontaneous clearance of hepatitis C virus (HCV) infection and with response to interferon-based antiviral treatment. Here, we evaluate the associations between IFN- {lambda} polymorphism and HCV variation through a genome-to-genome analysis in 8,729 patients from diverse ancestral backgrounds infected with various HCV genotypes. We searched for associations between rs12979860 genotype, a tag for IFN-{lambda} haplotypes, and amino acid variants in the NS3, NS4A, NS5A and NS5B HCV proteins. We report multiple associations between host and pathogen variants in the full cohort as well as in subgroups defined by viral genotype and human ancestry. We also assess the combined impact of human and HCV variation on pre-treatment viral load. By demonstrating that IFN-{lambda} genetic variation leaves a large footprint in the viral genome, this study provides strong evidence of pervasive viral adaptation to host innate immune pressure during chronic HCV infection.

genomics↗