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International Journal of Molecular... Jun 2024This paper presents the work performed to transition a lab-scale synthesis (1 g) to a large-scale (400 g) synthesis of the 3-5-diamino-1H-Pyrazole Disperazol, a new...
This paper presents the work performed to transition a lab-scale synthesis (1 g) to a large-scale (400 g) synthesis of the 3-5-diamino-1H-Pyrazole Disperazol, a new pharmaceutical for treatment of antibiotic-resistant biofilm infections. The potentially hazardous diazotisation step in the lab-scale synthesis was transformed to a safe and easy-to-handle flow chemistry step. Additionally, the paper presents an OSHA-recommended safety assessment of active compound , as performed by Fauske and Associates, LLC, Burr Ridge, IL, USA.
Topics: Pyrazoles; Pseudomonas aeruginosa; Anti-Bacterial Agents; Biofilms; Humans; Pseudomonas Infections; Risk Assessment
PubMed: 38928443
DOI: 10.3390/ijms25126737 -
Antibiotics (Basel, Switzerland) Jun 2024The airborne transmission of bacterial pathogens poses a significant challenge to public health, especially with the emergence of antibiotic-resistant strains. This...
The airborne transmission of bacterial pathogens poses a significant challenge to public health, especially with the emergence of antibiotic-resistant strains. This study investigated environmental factors influencing the survival of airborne bacteria, focusing on the effects of different carbon dioxide (CO) and dust concentrations. The experiments were conducted in an atmospheric simulation chamber using the non-resistant wild-type K12 (JM109) and a multi-resistant variant (JM109-pEC958). Different CO (100 ppm, 800 ppm, 3000 ppm) and dust concentrations (250 µg m, 500 µg m, 2000 µg m) were tested to encompass a wide range of CO and dust levels. The results revealed that JM109-pEC958 exhibited greater resilience to high CO and dust concentrations compared to its non-resistant counterpart. At 3000 ppm CO, the survival rate of JM109 was significantly reduced, while the survival rate of JM109-pEC958 remained unaffected. At the dust concentration of 250 µg m, JM109 exhibited significantly reduced survival, whereas JM109-pEC958 did not. When the dust concentration was increased to 500 and 2000 µg m, even the JM109-pEC958 experienced substantially reduced survival rates, which were still significantly higher than those of its non-resistant counterpart at these concentrations. These findings suggest that multi-resistant strains possess mechanisms enabling them to endure extreme environmental conditions better than non-resistant strains, potentially involving regulatory genes or efflux pumps. The study underscores the importance of understanding bacterial adaptation strategies to develop effective mitigation approaches against antibiotic-resistant bacteria in atmospheric environments. Overall, this study provides valuable insights into the interplay between environmental stressors and bacterial survival, serving as a foundational step towards elucidating the adaptation mechanisms of multi-resistant bacteria and informing strategies for combating antibiotic resistance in the atmosphere.
PubMed: 38927224
DOI: 10.3390/antibiotics13060558 -
Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2024To investigate the efficacy and safety of subcutaneous immunotherapy (SCIT) using dust mites in children with allergic asthma. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To investigate the efficacy and safety of subcutaneous immunotherapy (SCIT) using dust mites in children with allergic asthma.
METHODS
In a prospective randomized controlled study, 98 children with dust mite-induced allergic asthma were randomly divided into a control group (=49) and an SCIT group (=49). The control group received inhaled corticosteroid treatment, while the SCIT group additionally received a standardized three-year SCIT regimen. The two groups were compared based on peripheral blood eosinophil percentage, visual analogue score (VAS), total medication score, Asthma Control Test/Childhood Asthma Control Test scores, fractional exhaled nitric oxide (FeNO), and lung function before treatment, and at 6 months, 1 year, 2 years, and 3 years after treatment. Adverse reactions were recorded post-injection to evaluate the safety of SCIT.
RESULTS
Compared with pre-treatment levels, the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils, VAS, total medication score, and FeNO, while lung function significantly improved, and asthma control levels were better 3 years after treatment (<0.05). Compared with the control group, the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment (<0.05). A total of 2 744 injections were administered, resulting in 157 cases (5.72%) of local adverse reactions and 4 cases (0.15%) of systemic adverse reactions, with no severe systemic adverse events.
CONCLUSIONS
SCIT is an effective and safe treatment for allergic asthma in children.
Topics: Humans; Asthma; Male; Child; Female; Animals; Prospective Studies; Injections, Subcutaneous; Pyroglyphidae; Child, Preschool; Desensitization, Immunologic; Adolescent
PubMed: 38926371
DOI: 10.7499/j.issn.1008-8830.2309137 -
The Science of the Total Environment Jun 2024Coal dust (CD) is a common pollutant, and epidemiological surveys indicate that long-term exposure to coal dust not only leads to the occurrence of pulmonary diseases...
Coal dust (CD) is a common pollutant, and epidemiological surveys indicate that long-term exposure to coal dust not only leads to the occurrence of pulmonary diseases but also has certain impacts on cognitive abilities. However, there is little open-published literature on the effects and specific mechanisms of coal dust exposure on the cognition of patients with Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). An animal model has been built in this study with clinical population samples to explore the changes in neuroinflammation and cognitive abilities with coal dust exposure. In the animal model, compared to C57BL/6 mice, APP/PS1 mice exposed to coal dust exhibited more severe cognitive impairment, accompanied by significantly elevated levels of neuroinflammatory factors Apolipoprotein E4 (AOPE4) and Interleukin-6 (IL6) in the hippocampus, and more severe neuronal damage. In clinical sample sequencing, it was found that there is significant upregulation of AOPE4, neutrophils, and IL6 expression in the peripheral blood of MCI patients compared to normal individuals. Mechanistically, cell experiments revealed that IL6 could promote the phosphorylation of ERK1/2 and enhance the expression of transcription factor SP1, thereby promoting AOPE4 expression. The results of this study suggest that coal dust can promote the upregulation of IL6 and AOPE4 in patients, exacerbating cognitive impairment.
PubMed: 38925396
DOI: 10.1016/j.scitotenv.2024.174202 -
Environmental Pollution (Barking, Essex... Jun 2024This study investigates river dust episodes along the Choshui and Kaoping Rivers in Taiwan, focusing on their spatiotemporal distribution and correlation with...
This study investigates river dust episodes along the Choshui and Kaoping Rivers in Taiwan, focusing on their spatiotemporal distribution and correlation with hydrometeorological factors (temperature, precipitation, relative humidity, and wind speed). Using the Improved Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (ICEEMDAN) algorithm and time-dependent intrinsic correlation (TDIC) analysis, we identified significant annual and diurnal correlations between PM10 concentrations and these factors. The analysis revealed that wind speed at Lunbei station had a positive annual correlation with PM10, while other factors exhibited significant negative correlations. Seasonal variations in PM10 correlations with temperature, relative humidity, and wind speed were observed, aligning with the prevailing seasons of river dust episodes. Wind motion analysis highlighted diurnal associations with land-sea breezes and annual correlations with the winter monsoon. Specifically, the Choshui River's dust events coincided with the northeast monsoon, whereas the Kaoping River's events occurred during the northwest and southwest monsoons. The study also uncovered that downstream stations (Lunbei and Daliao) were more prone to severe dust events than upstream stations (Douliu and Pingtung). These findings enhance our understanding of the dynamics and environmental impacts of river dust episodes, providing valuable insights for air quality management and health risk mitigation.
PubMed: 38925217
DOI: 10.1016/j.envpol.2024.124398 -
International Journal of Biological... Jun 2024Chemical dust suppression is typically associated with high economic costs, unclear efficacy, and poor degradability. In this study, sodium alginate (SA) was extracted...
Chemical dust suppression is typically associated with high economic costs, unclear efficacy, and poor degradability. In this study, sodium alginate (SA) was extracted from kelp and cross-linked with polyvinyl alcohol (PVA) and polyacrylamide (PAM). Sulfonated castor oil (CAS) was subsequently added to generate a three-dimensional network hydrogel dust suppressant (PVA-SA-PAM/CAS). Using single-factor experiments, the optimal reaction temperature (60 °C) and dosages of PVA, PAM, and the cross-linking agent (2.5, 4.5, and 0.1 g, respectively) were determined. The viscosity and compressive strength of the prepared hydrogel were 86 mPa·s and 218 kPa, respectively, which meet the requirements for mine dust suppression. Various analyses revealed the hydrogel's reaction process and microstructure changes. Additionally, thermogravimetric experiments proved that the hydrogel had good thermal stability. The specific surface area and pore size of the hydrogel were 0.0278 m/g and 11.8 nm, respectively, improving its adsorption capacity. Additionally, PVA-SA-PAM/CAS exhibited a good water retention rate. The dust suppression efficiency of PVA-SA-PAM/CAS was >98 % under strong winds (12 m/s). Moreover, the degradation rate of PVA-SA-PAM/CAS was 37 % after eight cycles (56 d) under environmental conditions. Therefore, PVA-SA-PAM/CAS exhibits good wetting, dust suppression, and degradation properties, which can effectively alleviate mine dust pollution.
PubMed: 38925185
DOI: 10.1016/j.ijbiomac.2024.133408 -
Environmental Science & Technology Jun 2024
Rebuttal to Correspondence on "First Evidence of Hindered Amine Light Stabilizers As Abundant, Ubiquitous, Emerging Pollutants in Dust and Air Particles: A New Concern for Human Health".
PubMed: 38924476
DOI: 10.1021/acs.est.4c05566 -
Environmental Science & Technology Jun 2024
Correspondence on "First Evidence of Hindered Amine Light Stabilizers as Abundant, Ubiquitous, Emerging Pollutants in Dust and Air Particles: A New Concern for Human Health".
PubMed: 38924468
DOI: 10.1021/acs.est.4c04400 -
Immunology and Cell Biology Jun 2024Eosinophils play divergent roles in health and disease, contributing to both immunoregulatory and proinflammatory responses. Helminth infection is strongly associated...
Eosinophils play divergent roles in health and disease, contributing to both immunoregulatory and proinflammatory responses. Helminth infection is strongly associated with eosinophilia and the induction of the type 2 cytokines interleukin (IL)-5, IL-4 and IL-13. This study aimed to elucidate the heterogeneity of pulmonary eosinophils in response to helminth infection and the roles of IL-5, IL-4 and IL-13 in driving pulmonary eosinophil responses. Using the murine helminth model Nippostrongylus brasiliensis (Nb), we characterize a subtype of eosinophils, defined by high expression of CD101, that is induced in the lungs of Nb-infected mice and are phenotypically distinct from lung eosinophils that express low levels of CD101. Strikingly, we show that the two eosinophil subtypes have distinct anatomical localization within the lung: CD101 eosinophils are predominantly localized in the lung vasculature, whereas Nb-induced CD101 eosinophils are predominantly localized in the extravascular lung niche. We show that CD101 eosinophils are also induced across other models of pulmonary infection and inflammation, including a nonlung-migrating helminth infection, house dust mite-induced allergic inflammation and influenza infection. Furthermore, we demonstrate that the induction of CD101 tissue eosinophils is independent of IL-5 and IL-4 signaling, but is dependent on intact IL-13 signaling. These results suggest that IL-13 produced during helminth infection and other disease states promotes a pulmonary tissue-infiltrating program in eosinophils defined by high expression of CD101.
PubMed: 38924182
DOI: 10.1111/imcb.12796 -
Proceedings of the National Academy of... Jul 2024Asthma is a widespread airway disorder where GATA3-dependent Type-2 helper T (Th2) cells and group 2 innate lymphoid cells (ILC2s) play vital roles. Asthma-associated...
Asthma is a widespread airway disorder where GATA3-dependent Type-2 helper T (Th2) cells and group 2 innate lymphoid cells (ILC2s) play vital roles. Asthma-associated single nucleotide polymorphisms (SNPs) are enriched in a region located 926-970 kb downstream from GATA3 in the 10p14 (hG900). However, it is unknown how hG900 affects the pathogenesis of allergic airway inflammation. To investigate the roles of the asthma-associated GATA3 enhancer region in experimental allergic airway inflammation, we first examined the correlation between GATA3 expression and the activation of the hG900 region was analyzed by flow cytometry and ChIP-qPCR. We found that The activation of enhancers in the hG900 region was strongly correlated to the levels of GATA3 in human peripheral T cell subsets. We next generated mice lacking the mG900 region (mG900KO mice) were generated by the CRISPR-Cas9 system, and the development and function of helper T cells and ILCs in mG900KO mice were analyzed in steady-state conditions and allergic airway inflammation induced by papain or house dust mite (HDM). The deletion of the mG900 did not affect the development of lymphocytes in steady-state conditions or allergic airway inflammation induced by papain. However, mG900KO mice exhibited reduced allergic inflammation and Th2 differentiation in the HDM-induced allergic airway inflammation. The analysis of the chromatin conformation around by circular chromosome conformation capture coupled to high-throughput sequencing (4C-seq) revealed that the mG900 region interacted with the transcription start site of with an influencing chromatin conformation in Th2 cells. These findings indicate that the mG900 region plays a pivotal role in Th2 differentiation and thus enhances allergic airway inflammation.
Topics: GATA3 Transcription Factor; Animals; Th2 Cells; Mice; Cell Differentiation; Asthma; Enhancer Elements, Genetic; Humans; Mice, Knockout; Inflammation; Hypersensitivity; Polymorphism, Single Nucleotide; Mice, Inbred C57BL
PubMed: 38923989
DOI: 10.1073/pnas.2320727121