ABSTRACT
BACKGROUND: To analyze the risk factors for the development of avascular necrosis (AVN) of the femoral head after reduction surgery in children with developmental hip dysplasia (DDH), and to establish a prediction nomogram. METHODS: The clinical data of 134 children with DDH (169 hips) treated with closure reduction or open reduction from December 2016 to December 2019 were retrospectively analyzed. Independent risk factors for AVN after DDH reduction being combined with cast external immobilization were determined by univariate analysis and multivariate logistic regression and used to generate nomograms predicting the occurrence of AVN. RESULTS: A total of 169 hip joints in 134 children met the inclusion criteria, with a mean age at surgery of 10.7 ± 4.56 months (range: 4-22 months) and a mean follow-up duration of 38.32 ± 27.00 months (range: 12-94 months). AVN developed in 42 hip joints (24.9%); univariate analysis showed that the International Hip Dysplasia Institute (IHDI) grade, preoperative development of the femoral head ossification nucleus, cartilage acetabular index, femoral head to acetabular Y-shaped cartilage distance, residual acetabular dysplasia, acetabular abduction angle exceeding 60°, and the final follow-up acetabular index (AI) were associated with the development of AVN (P < 0.05). Multivariate logistic regression analysis showed that the preoperative IHDI grade, development of the femoral head ossification nucleus, acetabular abduction angle exceeding 60°, and the final follow-up AI were independent risk factors for AVN development (P < 0.05). Internal validation of the Nomogram prediction model showed a consistency index of 0.833. CONCLUSION: Preoperative IHDI grade, preoperative development of the femoral head ossification nucleus, final AI, and acetabular abduction angle exceeding 60° are risk factors for AVN development. This study successfully constructed a Nomogram prediction model for AVN after casting surgery for DDH that can predict the occurrence of AVN after casting surgery for DDH.
Subject(s)
Developmental Dysplasia of the Hip , Femur Head Necrosis , Nomograms , Humans , Male , Female , Femur Head Necrosis/etiology , Femur Head Necrosis/surgery , Femur Head Necrosis/diagnostic imaging , Risk Factors , Retrospective Studies , Developmental Dysplasia of the Hip/surgery , Developmental Dysplasia of the Hip/diagnostic imaging , Infant , Femur Head/surgery , Femur Head/diagnostic imaging , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Hip Dislocation, Congenital/surgery , Hip Dislocation, Congenital/diagnostic imaging , Follow-Up StudiesABSTRACT
OBJECTIVE: Endothelial cells play a critical role in maintaining vascular function and kinetic homeostasis, but excessive accumulation of palmitic acid (PA) may lead to endoplasmic reticulum stress and trigger endothelial cell dysfunction. Baicalin (BCL), a natural plant extract, has received widespread attention for its biological activities in anti-inflammation and anti-oxidative stress. However, the mechanism of BCL on PA-induced endothelial cell dysfunction is unclear. Therefore, the aim of this study was to investigate whether BCL could inhibit PA-induced endoplasmic reticulum stress and thus attenuate endothelial cell dysfunction. METHODS: Human umbilical vein endothelial cells (HUVECs) were divided into Control, PA, PAâ+âBCL-10 µM, PAâ+âBCL-20 µM, and PAâ+âBCL-50 µM groups. The PA group was treated with PA (200 µM), while the PAâ+âBCL groups were co-treated with different concentrations of BCL (10 µM, 20 µM, 50 µM) for 24âhours. Cell viability was detected by MTT. Cell migration ability was determined by Transwell assay, apoptosis level by flow cytometry, and tube formation ability by tube formation assay. Finally, the levels of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and angiogenesis-related proteins (VEGFA and FGF2) were detected by western blot, MMP-9, as well as the protein levels of endoplasmic reticulum stress biomarkers (GRP78, CHOP, PERK, and ATF4). RESULTS: The results at the cellular level showed that cell viability, migration ability and tube formation ability of PA-induced HUVECs were significantly reduced, while apoptosis level was significantly increased. However, administration of different concentrations of BCL significantly enhanced PA-induced cell viability, migration ability and tube formation ability of HUVECs while inhibiting apoptosis. The results of protein levels showed that the protein levels of Bax and cleaved caspase-3 were observably up-regulated in the cells of the PA group, while the protein level of Bcl-2 was significantly down-regulated; compared with the PA group, the protein levels of Bax and cleaved caspase-3 were much lower and the Bcl-2 protein level was much higher in the PAâ+âBCL group. Additionally, the protein levels of VEGFA, FGF2 and MMP-9 were raised and those of GRP78, CHOP, PERK and ATF4 were lowered in the PAâ+âBCL group of cells in a concentration-dependent manner. CONCLUSION: BCL significantly attenuates PA-induced endothelial cell dysfunction by inhibiting endoplasmic reticulum stress.
ABSTRACT
The impact of early life exposure to residential greenness on childhood rhinitis and its interaction with particulate matter (PM) of different size fractions remain inconsistent. Herein, we recruited 40,486 preschool children from randomly selected daycare centers in 7 cities in China from 2019 to 2020, and estimated exposure to residential greenness by the normalized difference vegetation index (NDVI) with a 500 m buffer. Exposure to ambient PM (PM1, PM2.5, and PM10) was evaluated using a satellite-based prediction model (daily, at a resolution of 1 km × 1 km). By mixed-effect logistic regression, NDVI values during pregnancy, in the first (0-1 year old) and the second (1-2 years old) year of life were negatively associated with lifetime rhinitis (LR) and current rhinitis (CR) (P < 0.001). PM in the same time windows was associated with increased risks of LR and CR in children, with smaller size fraction of PM showing greater associations. The negative associations between prenatal and postnatal NDVI and LR and CR in preschool children remained robust after adjusting for concomitant exposure to PM, whereas the associations of postnatal NDVI and rhinitis showed significant interactions with PM. At lower levels of PM, postnatal NDVI remained negatively associated with rhinitis and was partly mediated by PM (10.0-40.9 %), while at higher levels of PM, the negative associations disappeared or even turned positive. The cut-off levels of PM were identified for each size fraction of PM. In conclusion, prenatal exposure to greenness had robust impacts in lowering the risk of childhood rhinitis, while postnatal exposure to greenness depended on the co-exposure levels to PM. This study revealed the complex interplay of greenness and PM on rhinitis in children. The exposure time window in prenatal or postnatal period and postnatal concomitant PM levels played important roles in influencing the associations between greenness, PM and rhinitis.
Subject(s)
Air Pollutants , Environmental Exposure , Particulate Matter , Prenatal Exposure Delayed Effects , Rhinitis , Humans , Particulate Matter/analysis , China/epidemiology , Female , Child, Preschool , Rhinitis/epidemiology , Pregnancy , Air Pollutants/analysis , Infant , Environmental Exposure/statistics & numerical data , Prenatal Exposure Delayed Effects/epidemiology , Male , Air Pollution/statistics & numerical data , Infant, Newborn , Particle SizeABSTRACT
Allergic asthma is a chronic inflammatory airway disease with a high mortality rate and a rapidly increasing prevalence in recent decades that is closely linked to environmental change. Previous research found that high humidity (HH) and the traffic-related air pollutant NO2 both aggregated allergic asthma. Their combined effect and mechanisms on asthma exacerbation, however, are unknown. Our study aims to toxicologically clarify the role of HH (90%) and NO2 (5 ppm) on allergic asthma. Ninety male Balb/c mice were randomly assigned to one of six groups (n = 15 in each): saline control, ovalbumin (OVA)-sensitized, OVA + HH, OVA + NO2, OVA + HH + NO2, and OVA + HH + NO2+Capsazepine (CZP). After 38 days of treatment, the airway function, pathological changes in lung tissue, blood inflammatory cells, and oxidative stress and inflammatory biomarkers were comprehensively assessed. Co-exposure to HH and NO2 exacerbated histopathological changes and airway hyperresponsiveness, increased IgE, oxidative stress markers malonaldehyde (MDA) and allergic asthma-related inflammation markers (IL-1ß, TNF-α and IL-17), and upregulated the expressions of the transient receptor potential (TRP) ion channels (TRPA1, TRPV1 and TRPV4). Our findings show that co-exposure to HH and NO2 disrupted the Th1/Th2 immune balance, promoting allergic airway inflammation and asthma susceptibility, and increasing TRPV1 expression, whereas CZP reduced TRPV1 expression and alleviated allergic asthma symptoms. Thus, therapeutic treatments that target the TRPV1 ion channel have the potential to effectively manage allergic asthma.
Subject(s)
Air Pollutants , Asthma , Humidity , Lung , Mice, Inbred BALB C , Nitrogen Dioxide , Oxidative Stress , TRPV Cation Channels , Animals , Asthma/metabolism , Oxidative Stress/drug effects , Male , Mice , TRPV Cation Channels/metabolism , TRPV Cation Channels/genetics , Lung/drug effects , Lung/immunology , Lung/metabolism , Air Pollutants/toxicity , Nitrogen Dioxide/toxicity , Inflammation/metabolism , TRPA1 Cation Channel/metabolism , TRPA1 Cation Channel/genetics , Immunoglobulin E , Capsaicin/analogs & derivativesABSTRACT
BACKGROUND: Increasing studies linked outdoor air pollution (OAP), indoor environmental factors (IEFs), and antibiotics use (AU) with the first wave of allergies (i.e., asthma, allergic rhinitis, and eczema), yet the role of their exposures on children's second wave of allergy (i.e., food allergy) are unknown. OBJECTIVES: To investigate the association between exposure to OAP and IEFs and childhood doctor-diagnosed food allergy (DFA) during the pre-pregnancy, prenatal, early postnatal, and current periods, and to further explore the effect of OAP and IEFs on DFA in children co-exposed to antibiotics. METHODS: A retrospective cohort study involving 8689 preschoolers was carried out in Changsha, China. Data on the health outcomes, antibiotic use, and home environment of each child were collected through a questionnaire. Temperature and air pollutants data were obtained from 8 and 10 monitoring stations in Changsha, respectively. Exposure levels to temperature and air pollutants at individual home addresses were calculated by the inverse distance weighted (IDW) method. Multiple logistic regression models were employed to assess the associations of childhood DFA with exposure to OAP, IEF, and AU. RESULTS: Childhood ever doctor-diagnosed food allergy (DFA) was linked to postnatal PM10 exposure with OR (95% CI) of 1.18 (1.03-1.36), especially for CO and O3 exposure during the first year with ORs (95% CI) = 1.08 (1.00-1.16) and 1.07 (1.00-1.14), as well as SO2 exposure during the previous year with OR (95% CI) of 1.13 (1.02-1.25). The role of postnatal air pollution is more important for the risk of egg, milk and other food allergies. Renovation-related IAP (new furniture) and dampness-related indoor allergens exposures throughout all time windows significantly increased the risk of childhood DFA, with ORs ranging from 1.23 (1.03-1.46) to 1.54 (1.29-1.83). Furthermore, smoke-related IAP (environmental tobacco smoke [ETS], parental and grandparental smoking) exposure during pregnancy, first year, and previous year was related to DFA. Additionally, exposure to pet-related indoor allergens (cats) during first year and total plant-related allergens (particularly nonflowering plants) during previous year were associated with DFA. Moreover, exposure to plant-related allergy during first and previous year was specifically associated with milk allergy, while keeping cats during first year increased the risk of fruits/vegetables allergy. Life-time and early-life AU was associated with the increased risk of childhood DFA with ORs (95% CI) = 1.57 (1.32-1.87) and 1.46 (1.27-1.67), including different types food allergies except fruit/vegetable allergy. CONCLUSIONS: Postnatal OAP, life-time and early-life IEFs and AU exposure played a vital role in the development of DFA, supporting the "fetal origin of childhood FA" hypothesis.
Subject(s)
Anti-Bacterial Agents , Food Hypersensitivity , Humans , Female , Child, Preschool , Anti-Bacterial Agents/adverse effects , Male , Retrospective Studies , China/epidemiology , Pregnancy , Environmental Exposure/adverse effects , Infant , Air Pollutants/toxicity , Air Pollutants/adverse effects , Air Pollutants/analysis , Air Pollution/adverse effects , Air Pollution, Indoor/adverse effectsABSTRACT
γ-Aminobutyric acid (GABA) is a crucial neurotransmitter with wide application prospects. In this study, we focused on a GABA-producing strain from a traditional Chinese fermented beverage system. Among the six isolates, Lactobacillus hilgardii GZ2 exhibited the greatest ability to produce GABA in the traditional Chinese fermented beverage system. To increase GABA production, we optimized carbon sources, nitrogen sources, temperature, pH, and monosodium glutamate and glucose concentrations and conducted fed-batch fermentation. The best carbon and nitrogen sources for GABA production and cell growth were glucose, yeast extract and tryptone. Gradual increases in GABA were observed as the glucose and monosodium glutamate concentrations increased from 10 g/L to 50 g/L. During fed-batch fermentation, lactic acid was used to maintain the pH at 5.56, and after feeding with 0.03 g/mL glucose and 0.4 g/mL sodium glutamate for 72 h, the GABA yield reached 239 g/L. This novel high-GABA-producing strain holds great potential for the industrial production of GABA, as well as the development of health-promoting functional foods and medical fields.
Subject(s)
Lactobacillus , gamma-Aminobutyric Acid , Beverages , Fermentation , gamma-Aminobutyric Acid/biosynthesis , gamma-Aminobutyric Acid/metabolism , Glucose/metabolism , Hydrogen-Ion Concentration , Lactobacillus/metabolism , Lactobacillus/growth & development , Sodium Glutamate/metabolismABSTRACT
For texture control in plant-meat alternatives, the interrelationship between apparent characteristics and chemical bonds in high-fiber formulations remains unclear. The influence of mulberry leaf powder on apparent characteristics and chemical bonds of raw materials, block and strip products at addition amounts of 0.5-25% was analyzed. The results showed that 8% addition significantly increased the chewiness of the block by 98.12%. The strips' texture shows a downward trend, and the processing produced more redness and color difference. Additives promoted the formation of voids, lamellar and filamentous structures, and the strip produced more striped structures. Disulfide bonds significantly increased in the block, and the ß-turn in the secondary structure enhanced by 12.20%. The ß-turn transformed into a ß-sheet in strips. Principal component analysis revealed that the texture improvement was associated with producing disulfide bonds and ß-turn, providing a basis for high-fiber components to improve products' apparent characteristics by chemical bonds.
Subject(s)
Morus , Plant Leaves , Powders , Principal Component Analysis , Morus/chemistry , Plant Leaves/chemistry , Powders/chemistry , Food Handling , Meat Products/analysis , Plant Extracts/chemistry , Color , Animals , Meat SubstitutesABSTRACT
BACKGROUND: Few studies focus on the associations of green space composition and configuration with children's allergic rhinitis (AR). METHODS: A multi-center population-based cross-sectional study was performed in 7 cities in mainland of China between 2019 and 2020, recruiting 36,867 preschool children. Information on the current AR symptoms and demographics were collected by questionnaire. Exposure to residential greenness was estimated by Normalized Difference Vegetation Index (NDVI, 1000 m buffer) around the residences. Greenness composition was estimated in 3 main categories: forest, grassland, shrubland. Configuration of each category and total greenness (a spatial resolution of 10 m × 10 m) was estimated by 6 landscape pattern metrics to quantify their area, shape complexity, aggregation, connectivity, and patch density. Exposure to daily ambient particulate matter (PM1, PM2.5 and PM10, a spatial resolution of 1 km × 1 km) was estimated. Multilevel logistic regression models were applied to analyze the associations of greenness and its composition and configuration with AR, and mediation effects by PMs were examined by mediation analysis models. RESULTS: The prevalence of self-reported current AR in preschool children was 33.1%. Two indicators of forest, Aggregation Index of forest patches (AIforest) (odds ratio (OR):0.92, 95% Confidential Interval (CI): 0.88-0.97), and Patch Cohesion of forest (COHESIONforest) (OR: 0.93, 95% CI:0.89-0.98) showed significantly negative associations with AR symptoms. Mediation analyses found the associations were partially mediated by PMs. Age, exclusive breastfeed duration and season were the potential effect modifiers. The associations varied across seven cities. CONCLUSION: Our findings suggest the inverse associations of the aggregation and connectivity of forest patches surrounding residence addresses with AR symptoms. Since the cross-sectional study only provides associations rather than causation, further studies are needed to confirm our results as well as the underlying mechanisms.
Subject(s)
Cities , Rhinitis, Allergic , Rhinitis, Allergic/epidemiology , Child, Preschool , Humans , Cross-Sectional Studies , Male , China/epidemiology , Female , Environmental Exposure , Particulate Matter/analysis , Air Pollutants/analysis , PrevalenceABSTRACT
The biofilm of an engineered strain is limited by slow growth and low yield, resulting in an unsatisfactory ability to resist external stress and promote catalytic efficiency. Here, biofilms used as robust living catalysts were manipulated through dual functionalized gene regulation and carrier modification strategies. The results showed that gene overexpression regulates the autoinducer-2 activity, extracellular polymeric substance content and colony behavior of Escherichia coli, and the biofilm yield of csgD overexpressed strains increased by 79.35 % compared to that of the wild type strains (p < 0.05). In addition, the hydrophilicity of polyurethane fibres modified with potassium dichromate increased significantly, and biofilm adhesion increased by 105.80 %. Finally, the isoquercitrin yield in the catalytic reaction of the biofilm reinforced by the csgD overexpression strain and the modified carrier was 247.85 % higher than that of the untreated group. Overall, this study has developed engineered strains biofilm with special functions, providing possibilities for catalytic applications.
Subject(s)
Escherichia coli Proteins , Escherichia coli Proteins/genetics , Extracellular Polymeric Substance Matrix/metabolism , Gene Expression Regulation, Bacterial , Biofilms , Escherichia coli/genetics , Bacterial Proteins/metabolismABSTRACT
MOTIVATION: Retrosynthesis is a critical task in drug discovery, aimed at finding a viable pathway for synthesizing a given target molecule. Many existing approaches frame this task as a graph-generating problem. Specifically, these methods first identify the reaction center, and break a targeted molecule accordingly to generate the synthons. Reactants are generated by either adding atoms sequentially to synthon graphs or by directly adding appropriate leaving groups. However, both of these strategies have limitations. Adding atoms results in a long prediction sequence that increases the complexity of generation, while adding leaving groups only considers those in the training set, which leads to poor generalization. RESULTS: In this paper, we propose a novel end-to-end graph generation model for retrosynthesis prediction, which sequentially identifies the reaction center, generates the synthons, and adds motifs to the synthons to generate reactants. Given that chemically meaningful motifs fall between the size of atoms and leaving groups, our model achieves lower prediction complexity than adding atoms and demonstrates superior performance than adding leaving groups. We evaluate our proposed model on a benchmark dataset and show that it significantly outperforms previous state-of-the-art models. Furthermore, we conduct ablation studies to investigate the contribution of each component of our proposed model to the overall performance on benchmark datasets. Experiment results demonstrate the effectiveness of our model in predicting retrosynthesis pathways and suggest its potential as a valuable tool in drug discovery. AVAILABILITY AND IMPLEMENTATION: All code and data are available at https://github.com/szu-ljh2020/MARS.
Subject(s)
Benchmarking , Drug Discovery , Reading FramesABSTRACT
Previous studies have reported the association between particulate matter (PM) and childhood allergic rhinitis (AR). However, it is unclear whether food allergy (FA) modifies the PM-AR association. We aimed at evaluating the effect of the modification of FA on PM-AR association in preschool children. We adopted a cross-sectional study and conducted a questionnaire survey among preschool children aged 3-6 years in 7 cities in China from June 2019 to June 2020 to collect information on AR and FA. We used a combination of multilevel logistic regression and restricted cubic spline functions to quantitatively assess whether FA modifies the associations between size-specific PM exposure (1 × 1 km) and the risk of AR. The adjusted odds ratios (ORs) for AR among the children with FA as per a 10 µg/m3 increase in early life PM1, PM2.5, and PM10 were significantly higher than the corresponding ORs among the children without FA [e.g., OR: 1.58, 95% CI: (1.32, 1.90) vs 1.29, 95% CI: (1.18, 1.41), per 10 µg/m3 increase in PM1]. The interactions between FA and size-specific PM exposure and their effects on AR were statistically significant (all p-int < 0.001). FA, as an important part of the allergic disease progression, may modify the PM-AR association in preschool children.
Subject(s)
Air Pollutants , Air Pollution , Food Hypersensitivity , Rhinitis, Allergic , Child , Child, Preschool , Humans , Particulate Matter/analysis , Air Pollutants/analysis , Cross-Sectional Studies , Rhinitis, Allergic/epidemiology , China/epidemiology , Environmental Exposure/analysis , Air Pollution/analysisABSTRACT
BACKGROUND: Airborne particulate matter pollution has been linked to occurrence of childhood allergic rhinitis (AR). However, the relationships between exposure to particulate matter with an aerodynamic diameter ≤1 µm (PM1) during early life (in utero and first year of life) and the onset of childhood AR remain largely unknown. This study aims to investigate potential associations of in utero and first-year exposures to size-segregated PMs, including PM1, PM1-2.5, PM2.5, PM2.5-10, and PM10, with childhood AR. METHODS: We investigated 29286 preschool children aged 3-6 years in 7 Chinese major cities during 2019-2020 as the Phase II of the China Children, Families, Health Study. Machine learning-based space-time models were utilized to estimate early-life residential exposure to PM1, PM2.5, and PM10 at 1 × 1-km resolutions. The concentrations of PM1-2.5 and PM2.5-10 were calculated by subtracting PM1 from PM2.5 and PM2.5 from PM10, respectively. Multiple mixed-effects logistic models were used to assess the odds ratios (ORs) and 95% confidence intervals (CIs) of childhood AR associated with per 10-µg/m3 increase in exposure to particulate air pollution during in utero period and the first year of life. RESULTS: Among the 29286 children surveyed (mean ± standard deviation, 4.9 ± 0.9 years), 3652 (12.5%) were reported to be diagnosed with AR. Average PM1 concentrations during in utero period and the first year since birth were 36.3 ± 8.6 µg/m3 and 33.1 ± 6.9 µg/m3, respectively. Exposure to PM1 and PM2.5 during pregnancy and the first year of life was associated with an increased risk of AR in children, and the OR estimates were higher for each 10-µg/m3 increase in PM1 than for PM2.5 (e.g., 1.132 [95% CI: 1.022-1.254] vs. 1.079 [95% CI: 1.014-1.149] in pregnancy; 1.151 [95% CI: 1.014-1.306] vs. 1.095 [95% CI: 1.008-1.189] in the first year of life). No associations were observed between AR and both pre- and post-natal exposure to PM1-2.5, indicating that PM1 rather than PM1-2.5 contributed to the association between PM2.5 and childhood AR. In trimester-stratified analysis, childhood AR was only found to be associated with exposure to PM1 (OR = 1.077, 95% CI: 1.027-1.128), PM2.5 (OR = 1.048, 95% CI: 1.018-1.078), and PM10 (OR = 1.032, 95% CI: 1.007-1.058) during the third trimester of pregnancy. Subgroup analysis suggested stronger PM-AR associations among younger (<5 years old) and winter-born children. CONCLUSIONS: Prenatal and postnatal exposures to ambient PM1 and PM2.5 were associated with an increased risk of childhood AR, and PM2.5-related hazards could be predominantly attributed to PM1. These findings highlighted public health significance of formulating air quality guideline for ambient PM1 in mitigating children's AR burden caused by particulate air pollution.
Subject(s)
Air Pollutants , Air Pollution , Rhinitis, Allergic , Child, Preschool , Pregnancy , Female , Humans , Particulate Matter/analysis , Air Pollutants/toxicity , Cross-Sectional Studies , Environmental Exposure/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Rhinitis, Allergic/etiology , Rhinitis, Allergic/chemically induced , China/epidemiology , Dust/analysisABSTRACT
BACKGROUND: Parasitic infections (PIs) are common and pose substantial health hazards in children globally, but the fundamental environmental variables exposure during crucial time window(s) are unclear. OBJECTIVES: To identify key indoor and outdoor environmental factors leading to childhood PIs throughout critical time window(s). METHODS: A combined cross-sectional and retrospective cohort study was performed on 8689 children residing in Changsha, China. Data was acquired pertaining to the health status and environmental exposure of the children in their homes. Personal exposure to outdoor air pollutants at the residential address during the preconceptional, perinatal, and postnatal periods was computed using data from ten air quality monitoring stations. An analysis of the relationships between childhood PIs and both indoor and outdoor factors was conducted using a multiple logistic regression model. RESULTS: Childhood PIs were associated with outdoor CO and ozone (O3) exposure during the 10th-12th months prior to pregnancy, with ORs (95 % CI) of 1.68 (1.24-2.27) and 1.60 (1.15-2.22), respectively; childhood PIs were also associated with CO exposure during one year prior to pregnancy and the first trimester in utero [ORs = 1.57 (1.14-2.15) and 1.52 (1.17-1.97)]. Childhood PIs were found to be associated with PM2.5 exposure during pregnancy and the first year, with odds ratios of 1.51 (1.14-2.00) and 1.95 (1.22-3.12) per IQR increase in pollutant exposure, respectively. Exposures to smoke, renovation-related indoor air pollution (IAP), dampness and plant-related indoor allergens in the early life and past year were all associated with childhood PI, with odds ratios (95 % CI) ranging from 1.40 (1.01-1.95) for environmental tobacco smoke (ETS) during pregnancy to 1.63 (1.12-2.37) for mold/damp stains in the past year. In terms of PI risk, the early life and present periods were critical time windows for outdoor and indoor exposures, respectively. Certain individuals were more vulnerable to the PI risk associated with both indoor and outdoor exposures. Antibiotic use during child's lifetime and early years increased and decreased the PI risk of exposure to outdoor and indoor environments, respectively. CONCLUSIONS: Exposure to outdoor air pollution in early life and indoor environments in the past year were found to be associated with childhood PI.
Subject(s)
Air Pollutants , Air Pollution, Indoor , Air Pollution , Pregnancy , Female , Humans , Child , Retrospective Studies , Cross-Sectional Studies , Air Pollution/adverse effects , Air Pollution/analysis , Air Pollutants/adverse effects , Air Pollutants/analysis , Air Pollution, Indoor/adverse effects , Air Pollution, Indoor/analysis , Environmental Exposure/analysisABSTRACT
BACKGROUND: The potential role of dermal exposure diisononyl phthalate (DINP) as an adjuvant in allergic inflammation and asthma has been suggested. However, the current findings do not provide enough evidence to support this claim. OBJECTIVES: The purpose of this investigation was to examine the impact and mechanisms of allergic asthma exacerbation through the dermal exposure to DINP. METHODS: The study was undertaken using OVA-sensitized mice. Lung histopathology and airway hyperreactivity (AHR) were assessed. Expression levels of immunoglobulins (t-IgE, OVA-IgE and OVA-IgG1), cytokines (IL-31, IL-4, IL-5, IL-6, IL-13 and INF-γ), and TRPV1 were measured. To investigate the mechanism by which allergic asthma worsens due to dermal exposure to DINP, the blockade analysis using the IL-31 antagonist SB-431542 and the TRPV1 antagonist capsazepine (CZP) were performed. RESULTS: The findings of the study revealed that the simultaneous exposure to DINP and OVA resulted in an increase in inspiratory resistance (Ri) and expiratory resistance (Re), a decrease in the minimum value of lung dynamic compliance (Cldyn), and worsened airway remodeling. Additionally, it was found that this exposure led to an increase in the levels of IL-31 and TRPV1, which are biomarkers of Th2 cytokines (IL-4, IL-5, IL-6, and IL-13), as well as immunoglobulins (Total IgE, OVA-lgE, and OVA-IgG1), while decreasing the biomarker of Th1 cytokines (IFN-γ). However, these impairments showed improvement after the administration of SB-431542 or CZP. CONCLUSION: The findings of this research indicate that the IL-31/TRPV1 pathway plays a moderating function in OVA-induced allergic asthma worsened by dermal exposure to DINP.
Subject(s)
Asthma , Benzamides , Dioxoles , Interleukin-13 , Phthalic Acids , TRPV Cation Channels , Mice , Animals , Ovalbumin/toxicity , Interleukin-13/toxicity , Interleukin-4/toxicity , Interleukin-4/metabolism , Mice, Inbred BALB C , Interleukin-5/toxicity , Interleukin-6 , Asthma/metabolism , Lung/pathology , Cytokines/metabolism , Immunoglobulin E , Immunoglobulin G , Bronchoalveolar Lavage FluidABSTRACT
Basic leucine zipper (bZIP) transcription factors (TFs) are one of the largest families involved in plant physiological processes such as biotic and abiotic responses, growth, and development, etc. In this study, 66 members of the bZIP family were identified in Bletilla striata, which were divided into 10 groups based on their phylogenetic relationships with AtbZIPs. A structural analysis of BsbZIPs revealed significant intron-exon differences among BsbZIPs. A total of 63 bZIP genes were distributed across 16 chromosomes in B. striata. The tissue-specific and germination stage expression patterns of BsbZIPs were based on RNA-seq. Stress-responsive expression analysis revealed that partial BsbZIPs were highly expressed under low temperatures, wounding, oxidative stress, and GA treatments. Furthermore, subcellular localization studies indicated that BsbZIP13 was localized in the nucleus. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays suggested that BsbZIP13 could interact with multiple BsSnRK2s. The results of this study provide insightful data regarding bZIP TF as one of the stress response regulators in B. striata, while providing a theoretical basis for transgenic and functional studies of the bZIP gene family in B. striata.
Subject(s)
Basic-Leucine Zipper Transcription Factors , Stress, Physiological , Phylogeny , Stress, Physiological/genetics , Basic-Leucine Zipper Transcription Factors/metabolism , Oxidative Stress , Introns/genetics , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression ProfilingABSTRACT
The high cell density, immobilization and stability of biofilms are ideal characteristics for bacteria in resisting antibiotic therapy. CsgD is a transcription activating factor that regulates the synthesis of curly fimbriae and cellulose in Escherichia coli, thereby enhancing bacterial adhesion and promoting biofilm formation. To investigate the role of CsgD in biofilm formation and stress resistance in bacteria, the csgD deletion mutant ΔcsgD was successfully constructed from the engineered strain E. coli BL21(DE3) using the CRISPR/Cas9 gene-editing system. The results demonstrated that the biofilm of ΔcsgD decreased by 70.07% (p < 0.05). Additionally, the mobility and adhesion of ΔcsgD were inhibited due to the decrease in curly fimbriae and extracellular polymeric substances. Furthermore, ΔcsgD exhibited a significantly decreased resistance to acid, alkali and osmotic stress conditions (p < 0.05). RNA-Seq results revealed 491 differentially expressed genes between the parent strain and ΔcsgD, with enrichment primarily observed in metabolism-related processes as well as cell membrane structure and catalytic activity categories. Moreover, CsgD influenced the expression of biofilm and stress response genes pgaA, motB, fimA, fimC, iraP, ompA, osmC, sufE and elaB, indicating that the CsgD participated in the resistance of E. coli by regulating the expression of biofilm and stress response. In brief, the transcription factor CsgD plays a key role in the stress resistance of E. coli, and is a potential target for treating and controlling biofilm.
Subject(s)
Escherichia coli Proteins , Escherichia coli , Escherichia coli/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Escherichia coli Proteins/genetics , Escherichia coli Proteins/metabolism , Bacterial Proteins/metabolism , Trans-Activators/metabolism , Gene Expression Regulation, Bacterial , Biofilms , Bacterial Outer Membrane Proteins/geneticsABSTRACT
BACKGROUND: Despite mounting evidence linking outdoor air pollution with otitis media (OM), the role of air pollutant(s) exposure during which critical window(s) on childhood OM remains unknown. OBJECTIVES: We sought to identify the key air pollutant(s) and critical window(s) associated with the onset and recurrent attacks of OM in kindergarten children. METHODS: A combined cross-sectional and retrospective cohort study involving 8689 preschoolers aged 3-6 years was performed in Changsha, China. From 2013-2020, data on air pollutants were collected from ambient air quality monitoring stations in Changsha, and the exposure concentration to each child at their home address was calculated using the inverse distance weighted (IDW) method. The relationship between air pollution and OM in kindergarten children was studied using multiple logistic regression models. RESULTS: Childhood lifetime OM was associated with PM2.5, SO2 and NO2, with ORs (95% CI) of 1.43 (1.19-1.71), 1.18 (1.01-1.37) and 1.18 (1.00-1.39) by per IQR increase in utero exposure and with PM2.5, PM2.5-10 and PM10, with ORs = 1.15 (1.00-1.32), 1.25 (1.13-1.40) and 1.49 (1.28-1.74) for entire post-natal exposure, respectively. The 2nd trimester in utero and the post-natal period, especially the 1st year, were key exposure time windows to PM2.5 and PM10 associated with lifetime OM and the onset of OM. Similarly, the 4th gestational month was a critical window for all pollutants except CO exposure in relation to lifetime OM and OM onset, but not recurrent OM attacks. PM2.5 exposure during the nine gestational months and PM10 exposure during the first three years had cumulative effects on OM development. Our subgroup analysis revealed that certain children were more susceptible to the OM risk posed by air pollution. CONCLUSIONS: Early-life exposure to air pollution, particularly PM2.5 during the middle of gestation and PM10 during the early post-natal period, was associated with childhood OM.
Subject(s)
Air Pollutants , Air Pollution , Otitis Media , Child , Humans , Retrospective Studies , Cross-Sectional Studies , Air Pollution/adverse effects , Air Pollution/analysis , Air Pollutants/toxicity , Air Pollutants/analysis , China/epidemiology , Nitrogen Dioxide , Otitis Media/epidemiology , Particulate Matter/toxicity , Particulate Matter/analysis , Environmental Exposure/analysisABSTRACT
Nitrogen dioxide (NO2) is a widespread air pollutant. Epidemiological evidence indicates that NO2 is associated with an increase of incidence rate and mortality of asthma, but its mechanism is still unclear. In this study, we exposed mice to NO2 (5 ppm, 4 h per day for 30 days) intermittently to investigate the development and potential toxicological mechanisms of allergic asthma. We randomly assigned 60 male Balb/c mice to four groups: saline control, ovalbumin (OVA) sensitization, NO2 alone, and OVA+NO2 groups. The involved mechanisms were found from the perspective of airway inflammation and oxidative stress. The results showed that NO2 exposure could aggravate lung inflammation in asthmatic mice, and airway remodeling was characterized by significant thickening of the airway wall and infiltration of inflammatory cells. Moreover, NO2 would aggravate the airway hyperresponsiveness (AHR), which is characterized by significantly elevated inspiratory resistance (Ri) and expiratory resistance (Re), as well as decreased dynamic lung compliance (Cldyn). In addition, NO2 exposure promoted pro-inflammatory cytokines (IL-6 and TNF-α) and serum immunoglobulin (IgE) production. The imbalance of Th1/Th2 cell differentiation (IL-4 increased, IFN-γ reduced, IL-4/IFN-γ significantly increased) played a key role in the inflammatory response of asthma under NO2 exposure. In a nutshell, NO2 exposure could promote allergic airway inflammation and increase asthma susceptibility. The levels of ROS and MDA among asthmatic mice exposed to NO2 increased significantly, while GSH levels sharply decreased. These findings may provide better toxicological evidence for the mechanisms of allergic asthma risk due to NO2 exposure.