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1.
Animals (Basel) ; 14(13)2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38997973

ABSTRACT

The Hepatitis E virus (HEV) causes acute and chronic Hepatitis E and is a global public health concern. HEV genotypes 3 (HEV-3) and 4 (HEV-4) are common to humans and animals, and domestic pigs and wild boars have been identified as the main reservoirs. However, limited information is available on the status of HEV infection in pigs, particularly in the Guangdong Province, China. This study aimed to investigate the seroprevalence of HEV in pig farms within the Guangdong Province. A total of 1568 serum samples were collected from 25 farms and tested for anti-HEV IgG antibodies. Enzyme-linked immunosorbent assay (ELISA) results revealed that 57.53% (902/1568) of serum samples from 24 farms (24/25, 96%) were positive for anti-HEV IgG antibodies. Year, season, region, and age were all linked risk factors for HEV in Guangdong, with season and region showing more significant impacts. The results showing a high seroprevalence of HEV confirmed its circulation among domestic pigs in the Guangdong Province, China. The presence of this antibody indicates that HEV infection was or is present on farms, posing a risk of zoonotic transmission of HEV from pigs to exposed workers and from pork or organs to consumption.

2.
Front Microbiol ; 15: 1413120, 2024.
Article in English | MEDLINE | ID: mdl-38966388

ABSTRACT

While poly (3-hydroxybutyrate) (PHB) holds promise as a bioplastic, its commercial utilization has been hampered by the high cost of raw materials. However, glycerol emerges as a viable feedstock for PHB production, offering a sustainable production approach and substantial cost reduction potential. Glycerol stands out as a promising feedstock for PHB production, offering a pathway toward sustainable manufacturing and considerable cost savings. The identification and characterization of strains capable of converting glycerol into PHB represent a pivotal strategy in advancing PHB production research. In this study, we isolated a strain, Ralstonia sp. RRA (RRA). The strain exhibits remarkable proficiency in synthesizing PHB from glycerol. With glycerol as the carbon source, RRA achieved a specific growth rate of 0.19 h-1, attaining a PHB content of approximately 50% within 30 h. Through third-generation genome and transcriptome sequencing, we elucidated the genome composition and identified a total of eight genes (glpR, glpD, glpS, glpT, glpP, glpQ, glpV, and glpK) involved in the glycerol metabolism pathway. Leveraging these findings, the strain RRA demonstrates significant promise in producing PHB from low-cost renewable carbon sources.

3.
Int J Psychophysiol ; 201: 112360, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38735630

ABSTRACT

Economic decision-making is pivotal to both human private interests and the national economy. People pursue fairness in economic decision-making, but a proposer's moral identity can influence fairness processing. Previous ERP studies have revealed that moral identity has an effect on fairness considerations in the Ultimatum Game (UG), but the findings are inconsistent. To address the issue, we revised the moral-related sentences and used the ERP technique to measure the corresponding neural mechanism. We have observed that the fairness effect in UG can be mirrored in both MFN and P300 changes, whereas the moral identity effect on fairness in UG can be reflected by MFN but not P300 changes. These findings indicate that the moral identity of the proposer can modulate fairness processing in UG. The current study opens new avenues for clarifying the temporal course of the relationship between the proposer's moral identity and fairness in economic decision-making, which is beneficial for understanding the influencing mechanism of fairness processing and fair allocations in complex social contexts.


Subject(s)
Decision Making , Evoked Potentials , Games, Experimental , Morals , Humans , Male , Young Adult , Female , Decision Making/physiology , Adult , Evoked Potentials/physiology , Electroencephalography , Brain/physiology
4.
Diabetes ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38775784

ABSTRACT

Mouse models are extensively utilized in metabolic studies. However, inherent differences between the species, notably their blood glucose levels, hampered data translation into clinical settings. In this study, we confirmed GLUT1 to be the predominantly expressed glucose transporter in both adult and fetal human ß cells. In comparison, GLUT2 is detected in a small yet significant subpopulation of adult ß cells and is expressed to a greater extent in fetal ß cells. Notably, GLUT1/2 expression in INS+ cells from human stem cell-derived islet-like clusters (SC-islets) exhibited a closer resemblance to that observed in fetal islets. Transplantation of primary human islets or SC-islets, but not murine islets, lowered murine blood glucose to the human glycemic range, emphasizing the critical role of ß cells in establishing species-specific glycemia. We further demonstrate the functional requirements of GLUT1 and GLUT2 in glucose uptake and insulin secretion through chemically inhibiting GLUT1 in primary islets and SCislets, and genetically disrupting GLUT2 in SC-islets. Finally, we developed a mathematical model to predict changes in glucose uptake and insulin secretion as a function of GLUT1/2 expression. Collectively, our findings illustrate the crucial roles of GLUTs in human ß cells, and identify them as key components in establishing species-specific glycemic setpoints.

5.
Biodes Res ; 6: 0031, 2024.
Article in English | MEDLINE | ID: mdl-38572349

ABSTRACT

Protein engineering aimed at increasing temperature tolerance through iterative mutagenesis and high-throughput screening is often labor-intensive. Here, we developed a deep evolution (DeepEvo) strategy to engineer protein high-temperature tolerance by generating and selecting functional sequences using deep learning models. Drawing inspiration from the concept of evolution, we constructed a high-temperature tolerance selector based on a protein language model, acting as selective pressure in the high-dimensional latent spaces of protein sequences to enrich those with high-temperature tolerance. Simultaneously, we developed a variant generator using a generative adversarial network to produce protein sequence variants containing the desired function. Afterward, the iterative process involving the generator and selector was executed to accumulate high-temperature tolerance traits. We experimentally tested this approach on the model protein glyceraldehyde 3-phosphate dehydrogenase, obtaining 8 variants with high-temperature tolerance from just 30 generated sequences, achieving a success rate of over 26%, demonstrating the high efficiency of DeepEvo in engineering protein high-temperature tolerance.

6.
bioRxiv ; 2023 Nov 29.
Article in English | MEDLINE | ID: mdl-37961332

ABSTRACT

Understanding diverse responses of individual cells to the same perturbation is central to many biological and biomedical problems. Current methods, however, do not precisely quantify the strength of perturbation responses and, more importantly, reveal new biological insights from heterogeneity in responses. Here we introduce the perturbation-response score (PS), based on constrained quadratic optimization, to quantify diverse perturbation responses at a single-cell level. Applied to single-cell transcriptomes of large-scale genetic perturbation datasets (e.g., Perturb-seq), PS outperforms existing methods for quantifying partial gene perturbation responses. In addition, PS presents two major advances. First, PS enables large-scale, single-cell-resolution dosage analysis of perturbation, without the need to titrate perturbation strength. By analyzing the dose-response patterns of over 2,000 essential genes in Perturb-seq, we identify two distinct patterns, depending on whether a moderate reduction in their expression induces strong downstream expression alterations. Second, PS identifies intrinsic and extrinsic biological determinants of perturbation responses. We demonstrate the application of PS in contexts such as T cell stimulation, latent HIV-1 expression, and pancreatic cell differentiation. Notably, PS unveiled a previously unrecognized, cell-type-specific role of coiled-coil domain containing 6 (CCDC6) in guiding liver and pancreatic lineage decisions, where CCDC6 knockouts drive the endoderm cell differentiation towards liver lineage, rather than pancreatic lineage. The PS approach provides an innovative method for dose-to-function analysis and will enable new biological discoveries from single-cell perturbation datasets.

7.
Front Microbiol ; 14: 1293363, 2023.
Article in English | MEDLINE | ID: mdl-38033593

ABSTRACT

Background: The increase in antibiotic resistance of bacteria has become a major concern in clinical treatment. Silver nanoparticles (AgNPs) have significant antibacterial effects against Streptococcus suis. Therefore, this study aimed to investigate the antibacterial activity and mechanism of action of AgNPs against multidrug-resistant S. suis. Methods: The effect of AgNPs on the morphology of multidrug-resistant S. suis was observed using scanning electron microscopy (SEM). Differentially expressed proteins were analyzed by iTRAQ quantitative proteomics, and the production of reactive oxygen species (ROS) was assayed by H2DCF-DA staining. Results: SEM showed that AgNPs disrupted the normal morphology of multidrug-resistant S. suis and the integrity of the biofilm structure. Quantitative proteomic analysis revealed that a large number of cell wall synthesis-related proteins, such as penicillin-binding protein and some cell cycle proteins, such as the cell division protein FtsZ and chromosomal replication initiator protein DnaA, were downregulated after treatment with 25 µg/mL AgNPs. Significant changes were also observed in the expression of the antioxidant enzymes glutathione reductase, alkyl hydroperoxides-like protein, α/ß superfamily hydrolases/acyltransferases, and glutathione disulfide reductases. ROS production in S. suis positively correlated with AgNP concentration. Conclusion: The potential antibacterial mechanism of AgNPs may involve disrupting the normal morphology of bacteria by inhibiting the synthesis of cell wall peptidoglycans and inhibiting the growth of bacteria by inhibiting the cell division protein FtsZ and Chromosomal replication initiator protein DnaA. High oxidative stress may be a significant cause of bacterial death. The potential mechanism by which AgNPs inhibit S. suis biofilm formation may involve affecting bacterial adhesion and interfering with the quorum sensing system.

8.
PLoS Biol ; 21(9): e3002285, 2023 09.
Article in English | MEDLINE | ID: mdl-37733785

ABSTRACT

The canonical glycolysis pathway is responsible for converting glucose into 2 molecules of acetyl-coenzyme A (acetyl-CoA) through a cascade of 11 biochemical reactions. Here, we have designed and constructed an artificial phosphoketolase (APK) pathway, which consists of only 3 types of biochemical reactions. The core enzyme in this pathway is phosphoketolase, while phosphatase and isomerase act as auxiliary enzymes. The APK pathway has the potential to achieve a 100% carbon yield to acetyl-CoA from any monosaccharide by integrating a one-carbon condensation reaction. We tested the APK pathway in vitro, demonstrating that it could efficiently catabolize typical C1-C6 carbohydrates to acetyl-CoA with yields ranging from 83% to 95%. Furthermore, we engineered Escherichia coli stain capable of growth utilizing APK pathway when glycerol act as a carbon source. This novel catabolic pathway holds promising route for future biomanufacturing and offering a stoichiometric production platform using multiple carbon sources.


Subject(s)
Aldehyde-Lyases , Carbon , Acetyl Coenzyme A , Carbon/metabolism , Aldehyde-Lyases/genetics , Aldehyde-Lyases/metabolism , Glucose/metabolism , Metabolic Engineering
9.
bioRxiv ; 2023 Jun 14.
Article in English | MEDLINE | ID: mdl-37398096

ABSTRACT

The mechanisms underlying the ability of embryonic stem cells (ESCs) to rapidly activate lineage-specific genes during differentiation remain largely unknown. Through multiple CRISPR-activation screens, we discovered human ESCs have pre-established transcriptionally competent chromatin regions (CCRs) that support lineage-specific gene expression at levels comparable to differentiated cells. CCRs reside in the same topological domains as their target genes. They lack typical enhancer-associated histone modifications but show enriched occupancy of pluripotent transcription factors, DNA demethylation factors, and histone deacetylases. TET1 and QSER1 protect CCRs from excessive DNA methylation, while HDAC1 family members prevent premature activation. This "push and pull" feature resembles bivalent domains at developmental gene promoters but involves distinct molecular mechanisms. Our study provides new insights into pluripotency regulation and cellular plasticity in development and disease. One sentence summary: We report a class of distal regulatory regions distinct from enhancers that confer human embryonic stem cells with the competence to rapidly activate the expression of lineage-specific genes.

10.
Mol Cell ; 83(14): 2398-2416.e12, 2023 07 20.
Article in English | MEDLINE | ID: mdl-37402365

ABSTRACT

Nuclear receptor-binding SET-domain protein 1 (NSD1), a methyltransferase that catalyzes H3K36me2, is essential for mammalian development and is frequently dysregulated in diseases, including Sotos syndrome. Despite the impacts of H3K36me2 on H3K27me3 and DNA methylation, the direct role of NSD1 in transcriptional regulation remains largely unknown. Here, we show that NSD1 and H3K36me2 are enriched at cis-regulatory elements, particularly enhancers. NSD1 enhancer association is conferred by a tandem quadruple PHD (qPHD)-PWWP module, which recognizes p300-catalyzed H3K18ac. By combining acute NSD1 depletion with time-resolved epigenomic and nascent transcriptomic analyses, we demonstrate that NSD1 promotes enhancer-dependent gene transcription by facilitating RNA polymerase II (RNA Pol II) pause release. Notably, NSD1 can act as a transcriptional coactivator independent of its catalytic activity. Moreover, NSD1 enables the activation of developmental transcriptional programs associated with Sotos syndrome pathophysiology and controls embryonic stem cell (ESC) multilineage differentiation. Collectively, we have identified NSD1 as an enhancer-acting transcriptional coactivator that contributes to cell fate transition and Sotos syndrome development.


Subject(s)
Nuclear Proteins , Sotos Syndrome , Animals , Humans , Nuclear Proteins/metabolism , Chromatin , Sotos Syndrome/genetics , Sotos Syndrome/metabolism , Histone Methyltransferases/genetics , Transcription Factors/genetics , Cell Differentiation/genetics , Mammals/metabolism , Histone-Lysine N-Methyltransferase/genetics
11.
J Cell Physiol ; 238(8): 1909-1920, 2023 08.
Article in English | MEDLINE | ID: mdl-37357506

ABSTRACT

Human embryonic stem cells (hESCs) have great potential for developmental biology and regenerative medicine. However, extensive apoptosis often occurs when hESCs respond to various stresses or injuries. Understanding the molecular control and identifying new factors associated with hESC survival are fundamental to ensure the high quality of hESCs. In this study, we report that PRPF8, an RNA spliceosome component, is essential for hESC survival. PRPF8 knockdown (KD) induces p53 protein accumulation and activates the p53 pathway, leading to apoptosis in hESCs. Strikingly, silencing of p53 rescues PRPF8 KD-induced apoptosis, indicating that PRPF8 KD triggers hESC apoptosis through activating the p53 pathway. In search for the mechanism by which p53 pathway is activated by PRPF8 KD, we find that PRPF8 KD alters alternative splicing of many genes, including PIRH2 which encodes an E3 ubiquitin ligase of p53. PIRH2 has several isoforms such as PIRH2A, PIRH2B, and PIRH2C. Intriguingly, PRPF8 KD specifically increases the transcript level of the PIRH2B isoform, which lacks a RING domain and E3 ligase activity. Functionally, PIRH2B KD partially rescues the reduction in cell numbers and upregulation of P21 caused by PRPF8 KD in hESCs. The finding suggests that PRPF8 controls alternative splicing of PIRH2 to maintain the balance of p53 pathway activity and survival of hESCs. The PRPF8/PIRH2/p53 axis identified here provides new insights into how p53 pathway and hESC survival are precisely regulated at multiple layers, highlighting an important role of posttranscriptional machinery in supporting hESC survival.


Subject(s)
Alternative Splicing , Tumor Suppressor Protein p53 , Humans , Alternative Splicing/genetics , Protein Isoforms/genetics , Protein Isoforms/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Ubiquitination
12.
bioRxiv ; 2023 May 03.
Article in English | MEDLINE | ID: mdl-37205540

ABSTRACT

Pluripotent stem cells are defined by both the ability to unlimitedly self-renew and differentiate to any somatic cell lineage, but understanding the mechanisms that control stem cell fitness versus the pluripotent cell identity is challenging. We performed four parallel genome-scale CRISPR-Cas9 screens to investigate the interplay between these two aspects of pluripotency. Our comparative analyses led to the discovery of genes with distinct roles in pluripotency regulation, including many mitochondrial and metabolism regulators crucial for stem cell fitness, and chromatin regulators that control stem cell identity. We further discovered a core set of factors that control both stem cell fitness and pluripotency identity, including an interconnected network of chromatin factors that safeguard pluripotency. Our unbiased and systematic screening and comparative analyses disentangle two interconnected aspects of pluripotency, provide rich datasets for exploring pluripotent cell identity versus self-renewal, and offer a valuable model for categorizing gene function in broad biological contexts.

13.
Environ Pollut ; 290: 117949, 2021 Dec 01.
Article in English | MEDLINE | ID: mdl-34438166

ABSTRACT

The domestic combustion of smoky (bituminous) coal in the Chinese counties of Xuanwei and Fuyuan, are responsible for some of the highest rates of lung cancer in the world. Cancer rates vary between coal producing regions (deposits) in the area, with coals from Laibin exhibiting particularly high risks and smokeless (anthracite) coal exhibiting lower risks. However, little information is available on the specific burning characteristics of coals from throughout the area. We conducted an extensive controlled burning experiment using coal from multiple deposits in either a traditional firepit or ventilated stove, accompanied by a detailed examination of time-weighted and real-time size-aggregated particle concentrations. Smoky coal caused higher particle concentrations of all sizes than smokeless coal, with variations observed by geological source. Virtually all particle emissions were in the PM2.5 fraction (98% - mass based), and 75% and 46% were in the PM1 and PM0.3 fraction respectively. Real-time concentrations of PM1 and PM0.1 peaked after coal was added and declined afterwards. Ventilation reduced particle concentrations by up to 15-fold and increased the coal burning rate by 1.9-fold. These findings may provide valuable insight for reducing exposure and adverse health effects associated with domestic coal combustion.


Subject(s)
Air Pollutants , Air Pollution, Indoor , Air Pollution , Air Pollutants/analysis , Air Pollution, Indoor/analysis , China , Coal/analysis , Cooking
14.
ACS Synth Biol ; 10(7): 1574-1586, 2021 07 16.
Article in English | MEDLINE | ID: mdl-34129323

ABSTRACT

Adaptive laboratory evolution (ALE) is a widely used and highly effective tool for improving microbial phenotypes and investigating the evolutionary roots of biological phenomena. Serving as the raw materials of evolution, mutations have been extensively utilized to increase the chances of engineering molecules or microbes with tailor-made functions. The generation of genetic diversity is therefore a core technology for accelerating ALE, and a high-quality mutant library is crucial to its success. Because of its importance, technologies for generating genetic diversity have undergone rapid development in recent years. Here, we review the existing techniques for the construction of mutant libraries, briefly introduce their mechanisms and applications, discuss ongoing and emerging efforts to apply engineering technologies in the construction of mutant libraries, and suggest future perspectives for library construction.


Subject(s)
Adaptation, Physiological , Genetic Variation , Microbiota , Mutagenesis
15.
Mol Plant ; 14(7): 1199-1209, 2021 07 05.
Article in English | MEDLINE | ID: mdl-33951484

ABSTRACT

Taxus, commonly known as yew, is a well-known gymnosperm with great ornamental and medicinal value. In this study, by assembling a chromosome-level genome of the Himalayan yew (Taxus wallichiana) with 10.9 Gb in 12 chromosomes, we revealed that tandem duplication acts as the driving force of gene family evolution in the yew genome, resulting in the main genes for paclitaxel biosynthesis, i.e. those encoding the taxadiene synthase, P450s, and transferases, being clustered on the same chromosome. The tandem duplication may also provide genetic resources for the nature to sculpt the core structure of taxoids at different positions and subsequently establish the complex pathway of paclitaxel by neofunctionalization. Furthermore, we confirmed that there are two genes in the cluster encoding isoenzymes of a known enzyme in the paclitaxel biosynthetic pathway. The reference genome of the Himalayan yew will serve as a platform for decoding the complete biosynthetic pathway of paclitaxel and understanding the chemodiversity of taxoids in gymnosperms.


Subject(s)
Genome, Plant , Paclitaxel/biosynthesis , Taxus/genetics , Chromosomes, Plant , Evolution, Molecular , Gene Duplication , Taxoids , Taxus/metabolism , Whole Genome Sequencing
16.
J Colloid Interface Sci ; 582(Pt B): 932-939, 2021 Jan 15.
Article in English | MEDLINE | ID: mdl-32927173

ABSTRACT

Quasi-solid-state potassium-ion batteries (QSPIBs) are regarded as one of the most promising safety-enhanced energy storage devices. Herein, a facile method for preparing a potassium-ion composite electrolyte membrane on a large scale is presented for the first time. The as-synthesized membrane displays excellent electrochemical stability, good mechanical flexibility, and high ionic conductivity (9.31 × 10-5 S cm-1 at 25 °C). Furthermore, QSPIBs prepared with this membrane and commercial raw material-based electrodes show superior electrochemical performance even at low temperatures (99.7 mAh g-1 at -20 °C for half QSPIBs and 90.7 mAh g-1 at -15 °C for full QSPIBs), and a promising rate performance (115.6 mAh g-1 for half QSPIBs and 90.9 mAh g-1 for full QSPIBs at 800 mA g-1). The reaction mechanism and structure evolution of a 3,4,9,10-perylene-tetracarboxylicacid-dianhydride (PTCDA) cathode is also systematically studied. The promising characteristics of the prepared low-cost quasi-solid-state potassium-ion batteries in this work open up new possibilities for safer and more durable batteries and a wide range of practical applications in the electronics industry.

17.
Environ Health ; 19(1): 78, 2020 07 03.
Article in English | MEDLINE | ID: mdl-32620109

ABSTRACT

BACKGROUND: Asthma patients suffer from periodic acute worsening of symptoms (i.e. loss of asthma control or exacerbations), triggered by a variety of exogenous stimuli. With the growing awareness that air pollutants impact respiratory diseases, we investigated whether particulate matter (PM) derived from various livestock farms (BioPM) differentially affected innate and oxidative stress responses in asthma and health. METHODS: Peripheral blood mononuclear cells (PBMCs), collected from patients sequentially before and during loss of asthma control and from healthy individuals, were exposed to BioPM collected from chicken, goat and pig farms (1 and 5 µg/ml), with or without pre-treatment with antioxidants. Cytokine release and oxidative stress were assessed. RESULTS: PBMCs produced IFNγ, IL-1ß, IL-10 and TNFα upon stimulation with BioPM, with that from pig farms inducing the highest cytokine levels. Overall, cytokine production was irrespective of the presence or state of disease. However, PBMCs from stable asthma patients upon exposure to the three BioPM showed more extreme TNFα responses than those from healthy subjects. Furthermore, PBMCs obtained during loss of asthma control that were exposed to BioPM from pig farms showed enhanced IFNγ release as well as decreased oxidative stress levels upon pre-treatment with N-acetylcysteine (NAC) compared to stable disease. NAC, but not superoxide dismutase and catalase, also counteracted BioPM-induced cytokine release, indicating the importance of intracellular reactive oxygen species in the production of cytokines. CONCLUSIONS: BioPM triggered enhanced pro-inflammatory responses by PBMCs from both healthy subjects and asthma patients, with those from patients during loss of asthma control showing increased susceptibility to BioPM from pig farms in particular.


Subject(s)
Air Pollutants/adverse effects , Cytokines/metabolism , Farms , Leukocytes, Mononuclear/chemistry , Oxidative Stress , Particulate Matter/adverse effects , Animals , Asthma/physiopathology , Chickens , Environmental Health , Goats , Livestock , Sus scrofa
18.
Inhal Toxicol ; 32(6): 265-277, 2020 05.
Article in English | MEDLINE | ID: mdl-32571132

ABSTRACT

Background: Inhalation exposure to biological particulate matter (BioPM) from livestock farms may provoke exacerbations in subjects suffering from allergy and asthma. The aim of this study was to use a murine model of allergic asthma to determine the effect of BioPM derived from goat farm on airway allergic responses.Methods: Fine (<2.5 µm) BioPM was collected from an indoor goat stable. Female BALB/c mice were ovalbumin (OVA) sensitized and challenged with OVA or saline as control. The OVA and saline groups were divided in sub-groups and exposed intranasally to different concentrations (0, 0.9, 3, or 9 µg) of goat farm BioPM. Bronchoalveolar lavage fluid (BALF), blood and lung tissues were collected.Results: In saline-challenged mice, goat farm BioPM induced 1) a dose-dependent increase in neutrophils in BALF and 2) production of macrophage inflammatory protein-3a. In OVA-challenged mice, BioPM induced 1) inflammatory cells in BALF, 2) OVA-specific Immunoglobulin (Ig)G1, 3) airway mucus secretion-specific gene expression. RNAseq analysis of lungs indicates that neutrophil chemotaxis and oxidation-reduction processes were the representative genomic pathways in saline and OVA-challenged mice, respectively.Conclusions: A single exposure to goat farm BioPM enhanced airway inflammation in both saline and OVA-challenged allergic mice, with neutrophilic response as Th17 disorder and eosinophilic response as Th2 disorder indicative of the severity of allergic responses. Identification of the mode of action by which farm PM interacts with airway allergic pathways will be useful to design potential therapeutic approaches.


Subject(s)
Air Pollutants/toxicity , Asthma , Goats , Particulate Matter/toxicity , Acute Disease , Allergens , Animals , Asthma/genetics , Asthma/immunology , Asthma/pathology , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Cytokines/immunology , Eosinophils/immunology , Farms , Female , Immunoglobulin E/blood , Immunoglobulin G/blood , Lung/immunology , Lung/pathology , Mice, Inbred BALB C , Neutrophils/immunology , Ovalbumin , Transcriptome
19.
World Allergy Organ J ; 13(4): 100114, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32256941

ABSTRACT

Effects of airborne biological particulate matter (BioPM; from livestock farms) on the pulmonary airways are not well studied. The aim of the present study was to investigate whether fine (<2.5 µm) BioPM derived from indoor animal stables (two chicken and two pig farms) could modify airway allergic responses by using a mouse model of allergic airway disease (allergic asthma). After intraperitoneal ovalbumin (OVA) sensitization mice were either intranasally challenged with OVA (allergic mice) or saline (non-allergic controls). Mice were also intranasally treated with farm-derived BioPM. Bronchoalveolar lavage fluid (BALF), blood and lung tissues were collected one day after intranasal exposure. BioPM from all the farms caused an acute neutrophilic inflammatory response in non-allergic mice. In allergic mice, BioPM derived from pig farm 2 induced a larger cellular inflammatory response than other farm-derived BioPM. All farm BioPM elicited Th17 cytokine (Interleukin (IL)-23) production except chicken farm 2, whereas Th2 cytokine (IL-5) increase was only induced by BioPM collected from chicken farm 2. These results indicate the exposure of BioPM from chicken and pig farms may cause the enhancement of airway allergic response in mice following exposure to OVA. More variation in the responses between farms was observed in allergic than non-allergic mice. Understanding the source and doses of BioPM that may affect the airway allergic response could help susceptible individuals to avoid worsening their respiratory diseases.

20.
Front Microbiol ; 11: 122, 2020.
Article in English | MEDLINE | ID: mdl-32117145

ABSTRACT

Fast response to environmental changes plays a key role in the transmission and pathogenesis of Yersinia enterocolitica. Osmoregulated periplasmic glucans (OPGs) are known to be involved in environmental perception of several Enterobacteriaceae pathogens; however, the biological function of OPGs in Y. enterocolitica is still unclear. In this study, we investigated the role of OPGs in Y. enterocolitica by deleting the opgGH operon encoding enzymes responsible for OPGs biosynthesis. Complete loss of OPGs in the ΔopgGH mutant resulted in decreased motility, c-di-GMP production, biofilm formation and smaller cell size, whereas the overproduction of OPGs through restoration of opgGH expression promoted c-di-GMP/biofilm production and increased antibiotic resistance of Y. enterocolitica. Gene expression analysis revealed that opgGH deletion reduced transcription of flhDC, ftsAZ, hmsT and hmsHFRS genes regulated by the Rcs phosphorelay system, whereas additional deletion of rcs family genes (rcsF, rcsC, or rcsB) reversed this effect and restored motility and c-di-GMP/biofilm production but further reduced cell size. Furthermore, disruption of the Rcs phosphorelay increased the motility and promoted the induction of biofilm and c-di-GMP production regulated by OPGs through upregulating the expression of flhDC, hmsHFRS, and hmsT. However, deletion of genes encoding the EnvZ/OmpR phosphorelay downregulated the flhDC, hmsHFRS and hmsT expression, leading to the decreased motility and prevented the induction of biofilm and c-di-GMP production regulated by OPGs. These results indicated that Rcs phosphorelay had the effect on OPGs-mediated functional responses in Y. enterocolitica. Our findings disclose part of the biological role of OPGs and the underlying molecular mechanisms associated with Rcs system in the regulation of the pathogenic phenotype in Y. enterocolitica.

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