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Chemosphere Jul 2024Food safety is closely linked to human health. Thiabendazole is widely used as a fungicide and deodorant on agricultural products like vegetables and fruits to prevent...
Food safety is closely linked to human health. Thiabendazole is widely used as a fungicide and deodorant on agricultural products like vegetables and fruits to prevent fungal infections during transport and storage. This study aims to investigate the toxicity and potential mechanisms of Thiabendazole using novel network toxicology and molecular docking techniques. First, the ADMETlab2.0 and ADMETsar databases, along with literature, predicted Thiabendazole's potential to induce cancer and liver damage. Disease target libraries were constructed using GeneCards and TCMIP databases, while Thiabendazole target libraries were constructed using Swiss Target Prediction and TCMIP databases. The Venn database identified potential targets associated with Thiabendazole-induced cancer and liver injury. Protein-protein interaction (PPI) networks were derived from the STRING database, and gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways were obtained from the DAVID database. Molecular docking assessed the binding affinity between Thiabendazole and core targets. The study revealed 29 potential targets for Thiabendazole-induced cancer and 30 potential targets for liver injury. PPI identified 5 core targets for Thiabendazole-induced cancers and 4 core targets for induced liver injury. KEGG analysis indicated that Thiabendazole might induce gastric and prostate cancer via cyclin-dependent kinase 2 (CDK2) and epidermal growth factor receptor (EGFR) targets, and liver injury through the same targets, with the p53 signaling pathway being central. GO analysis indicated that Thiabendazole-induced cancers and liver injuries were related to mitotic cell cycle G2/M transition and DNA replication. Molecular docking showed stable binding of Thiabendazole with core targets including CDK1, CDK2, EGFR, and checkpoint kinase 1 (CHEK1). These findings suggest Thiabendazole may affect the G2/M transition of the mitotic cell cycle through the p53 signaling pathway, potentially inducing cancer and liver injury. This study provides a theoretical basis for understanding the potential molecular mechanisms underlying Thiabendazole toxicity, aiding in the prevention and treatment of related diseases. Additionally, the network toxicology approach accelerates the elucidation of toxic pathways for uncharacterized agricultural chemicals.
PubMed: 38964723
DOI: 10.1016/j.chemosphere.2024.142711 -
Chemosphere Jul 2024Efficient dewatering of sewage sludge is an energy- and carbon-saving procedure for sludge treatment in wastewater treatment facilities. The ultrasound-coupled divalent...
Efficient dewatering of sewage sludge is an energy- and carbon-saving procedure for sludge treatment in wastewater treatment facilities. The ultrasound-coupled divalent iron ion activated persulfate process can effectively promote sludge dewatering and improve organic substance content. Under the action of ultrasound (US 50 w/L), divalent iron ions (Fe) 200 mg/g (TS), and persulfate (PDS) 200 mg/g (TS) for 60 min, the capillary suction time (CST) was reduced by 79.74%, and the moisture content of the dewatered sludge cake reached 56.51 wt%. The organic carbon content of treated sludge was also four times higher than the original sludge and types were richer in short-chain volatile species in US/Fe/PDS. Moreover, the correlation analysis found that the relationship of between CST and SV, Zeta and lactate dehydrogenase (LDH) were positive correlation, and the relationship of SCOD and TC were positively correlated with the PN (SB-EPS). Mechanistic studies showed that the US/Fe/PDS system could produce oxygen activators by US coupling Fe to strengthen the effect of activated PDS strongly, while the sulfate radicals (SO·) radical was a dominant role. The cracking mechanism is divided into two pathways effectively degraded the macromolecule EPS into a small-molecule acid and further reduced the water-holding interfacial affinity as follow: (1) the radical path dominated by hydroxyl radicals (·OH), SO·, and superoxide radical (O·); (2) the non-radicals dominated by monoclinic oxygen (O). Afterwards, the electrostatic force and interfacial free energy were reduced, resulting in enhanced self-flocculation and mobility to enhanced dewaterability. These findings demonstrated the US/Fe/PDS system had significant advantages in sludge cracking and provided theoretical support for its practical application.
PubMed: 38964722
DOI: 10.1016/j.chemosphere.2024.142727 -
Chemosphere Jul 2024In this study, a co-catalytic route was explored to enhance the photo-ozone catalytic degradation of volatile organic compounds (VOCs). NiCoO was loaded onto the surface...
In this study, a co-catalytic route was explored to enhance the photo-ozone catalytic degradation of volatile organic compounds (VOCs). NiCoO was loaded onto the surface of CeO nanoparticles to create a composite catalyst (10%NiCoO/CeO). The integration of NiCoO onto CeO enhanced the interaction between the catalyst and toluene, a representative VOC, resulting in significantly increased toluene adsorption without a corresponding increase in specific surface area. This integration also improved the utilization of charge carriers and conversion of ozone to O. Under visible light irradiation, HO accumulated charge carriers at 10%NiCoO/CeO's surface, facilitating both ozone utilization and toluene adsorption. Another benefit of NiCoO loading was its ability to enhance the conversion efficiency of solar energy. Consequently, the toluene removal and mineralization efficiencies of 10%NiCoO/CeO were enhanced by 182% and 309% compared to CeO, and by 201% and 357% compared to NiCoO, respectively. Overall, this study demonstrated a novel co-catalyst design strategy for enhancing the photo-ozone catalytic degradation of VOCs.
PubMed: 38964721
DOI: 10.1016/j.chemosphere.2024.142756 -
Chemosphere Jul 2024Endocrine disrupting chemicals are of concern because of possible human health effects, thus they are frequently included in biomonitoring studies. Current analytical...
Endocrine disrupting chemicals are of concern because of possible human health effects, thus they are frequently included in biomonitoring studies. Current analytical methods are focused on known chemicals and are incapable of identifying or quantifying other unknown chemicals and their metabolites. Non-targeted analysis (NTA) methods are advantageous since they allow for broad chemical screening, which provides a more comprehensive characterization of human chemical exposure, and can allow elucidation of metabolic pathways for unknown chemicals. There are still many challenges associated with NTA, which can impact the results obtained. The chemical space, i.e., the group of known and possible compounds within the scope of the method, must clearly be defined based on the sample preparation, as this is critical in identifying chemicals with confidence. Data acquisition modes and mobile phase additives used with liquid chromatography coupled to high-resolution mass-spectrometry can affect the chemicals ionized and structural identification based on the spectral quality. In this study, a sample preparation method was developed using a novel clean-up approach with CarbonS cartridges, for endocrine-disrupting chemicals in urine, including new bisphenol A analogues and benzophenone-based UV filters, like methyl bis (4-hydroxyphenyl acetate). The study showed that data dependent acquisition (DDA) had a lower identification rate (40%) at low spiking levels, i.e., 1 ng/mL, compared to data independent acquisition (DIA) (57%), when Compound Discoverer was used. In DDA, more compounds were identified using Compound Discoverer, with an identification rate of 95% when ammonium acetate was compared to acetic acid (82%) as a mobile phase additive. TraceFinder software had an identification rate of 53% at 1 ng/mL spiking level using the DDA data, compared to 40% using the DIA data. Using the developed method, 2,4 bisphenol F was identified for the first time in urine samples. The results show how NTA can provide human exposure information for risk assessment and regulatory action but standardized reporting of procedures is needed to ensure study results are reproducible and accurate.
PubMed: 38964720
DOI: 10.1016/j.chemosphere.2024.142754 -
Infectious Diseases Now Jul 2024To compare the supply of molnupiravir and nirmatrelvir/ritonavir in relation to patient characteristics and other co-prescribed medicines and to estimate the number of...
Supply of nirmatrelvir/ritonavir and molnupiravir for patients with COVID-19 in the first eight months since listing on the Australian Pharmaceutical Benefits Scheme: A retrospective observational study.
OBJECTIVES
To compare the supply of molnupiravir and nirmatrelvir/ritonavir in relation to patient characteristics and other co-prescribed medicines and to estimate the number of patients without contraindications to nirmatrelvir/ritonavir who were treated with molnupiravir.
STUDY DESIGN, SETTING
Retrospective observational study of patients identified in the Pharmaceutical Benefits Scheme (PBS) 10 % sample dataset who were supplied with either molnupiravir or nirmatrelvir/ritonavir between May and December 2022. We supplemented the PBS dataset with aggregated counts from published literature to determine prevalence of clinical contraindications to nirmatrelvir/ritonavir.
MAIN OUTCOME MEASURES
We used multivariable Poisson regression to estimate risk ratios (RR) of receiving nirmatrelvir/ritonavir over molnupiravir.
RESULTS
We identified 54,550 patients who received either nirmatrelvir/ritonavir (26.8 %) or molnupiravir (73.2 %). Their average age was 71.6 (SD = 13.4) years and 57.1 % were female. Patients were less likely to receive nirmatrelvir/ritonavir with increasing age (RR = 0.50; 95 % CI: 0.48-0.53; for ages 85 + compared to < 65 years) or who had received medicines contraindicated for use with nirmatrelvir/ritonavir (RR = 0.66; 95 % CI: 0.64-0.68). During the study period, we estimated that between 28.4 % and 45.4 % of patients aged ≥ 65 years had received molnupiravir in the absence of pharmacological and clinical contraindications to nirmatrelvir/ritonavir.
CONCLUSION
Many prescriptions were written for molnupiravir where there were no contraindications to nirmatrelvir/ritonavir. The benefits that followed from prompt government action in approving and obtaining nirmatrelvir/ritonavir were therefore likely to be less than they could potentially have been. Governments should consider investing in quality improvement systems to ensure the best outcomes in terms of efficacy and safety.
PubMed: 38964717
DOI: 10.1016/j.idnow.2024.104953 -
Journal of Cardiology Jul 2024Heart transplantation (HTx) is a definitive therapy for refractory heart failure. Cardiac allograft vasculopathy (CAV), characterized by diffuse arteriopathy involving...
BACKGROUND
Heart transplantation (HTx) is a definitive therapy for refractory heart failure. Cardiac allograft vasculopathy (CAV), characterized by diffuse arteriopathy involving the epicardial coronary arteries and microvasculature, is the major cause of death for patients with HTx. 13 N-ammonia positron emission tomography (NH3-PET) can offer diagnostic and prognostic utility for CAV. The splenic switch-off (SSO) detected in NH3-PET is a hemodynamic indicator of favorable response to adenosine. We hypothesized that both CAV and SSO reflected a pathology that progresses in parallel with systemic vascular endothelial dysfunction. Therefore, we quantitatively evaluated splenic adenosine reactivity measured using NH3-PET as an index of endothelial function, and examined its predictability for CAV.
METHODS
Forty-eight patients who underwent NH3-PET after HTx were analyzed. The spleen ratio was calculated as the mean standardized uptake value, measured by placing an ROI on the spleen, at stress divided by that at rest. SSO was defined by a cutoff determined using receiver operating characteristic (ROC) analysis for the spleen ratio. The endpoint was appearance or progression of CAV. Predictability of SSO was analyzed using Kaplan-Meier analysis.
RESULTS
The endpoint occurred in 9 patients during a mean follow-up of 45 ± 17 months. ROC curve analysis demonstrated a cutoff of 0.94 for spleen ratio. Patients without SSO displayed a significantly higher CAV rate than those with SSO (p = 0.022).
CONCLUSIONS
SSO reflects the endothelial function of systemic blood vessels and was a predictor of CAV in patients with HTx.
PubMed: 38964711
DOI: 10.1016/j.jjcc.2024.06.010 -
Comparative Biochemistry and... Jul 2024Comparative physiologists often compare physiological traits across organisms to understand the selective pressures influencing their evolution in different...
Comparative physiologists often compare physiological traits across organisms to understand the selective pressures influencing their evolution in different environments. Traditionally focused on the organisms themselves, comparative physiology has more recently incorporated studies of the microbiome-the communities of microbes living in and on animals that influence host physiology. In this commentary, we describe the utility of applying a comparative framework to study the microbiome, particularly in understanding how hosts vary in their dependence on microbial communities for physiological function, a concept we term the "microbial dependence continuum". This hypothesis suggests that hosts exist on a spectrum ranging from high to low reliance on their microbiota. Certain physiological traits may be highly dependent on microbes for proper function in some species but microbially independent in others. Comparative physiology can elucidate the selective pressures driving species along this continuum. Here, we discuss the microbial dependence continuum in detail and how comparative physiology can be useful to study it. Then, we discuss two example traits, herbivory and flight, where comparative physiology has helped reveal the selective pressures influencing host dependence on microbial communities. Lastly, we discuss useful experimental approaches for studying the microbial dependence continuum in a comparative physiology context.
PubMed: 38964709
DOI: 10.1016/j.cbpa.2024.111690 -
Neuroscience Letters Jul 2024Postural alignment is strongly shaped by inborn anatomical and nonvolitional neural factors, whereas postural stability is dynamic in nature and driven by both automatic... (Review)
Review
Postural alignment is strongly shaped by inborn anatomical and nonvolitional neural factors, whereas postural stability is dynamic in nature and driven by both automatic and volitional sensorimotor processes. The sensory and motor systems responsible for these functions are tightly integrated with the central nervous system, several vital structures of which are in close proximity to the stomatognathic system. Interventions in the oral cavity have therefore been stipulated to provide sensory feedback, which may then be translated into motor function. Since the early 90 s, numerous intervention studies have provided evidence of this correlation, with traditional views advocating that causative factors are mainly indirect. Dynamic postural responses were thus predominantly considered manifestations of head displacement, with most studies identifying potential connections along active and passive muscular interactions. The consideration however, that neuromuscular adaptations of whole-body dynamics might extend beyond biomechanical responses and involve direct pathways as well, has led to a recent paradigm shift, challenging conventional perspectives. Among the suggested pathways are central projections of trigeminal afferents, providing inputs for the oculomotor system, as well as active and passive muscular interactions. Further intervention studies indicate a sensory integration of the stomatognathic system to proprioception, likely through neural networks that work in concert with visual cues and the vestibular organs. Building on this accumulating pool of evidence, a timely perspective is provided on a critical yet underexplored aspect of neurophysiology: the intricate interplay between the cranio-cervico-mandibular system and the broader framework of body posture.
PubMed: 38964707
DOI: 10.1016/j.neulet.2024.137889 -
Brain Research Jul 2024Magnetic resonance imaging (MRI) brain abnormalities have been reported in the corpus callosum (CC) of patients with adult-onset hypothyroidism. However, no study has...
BACKGROUND
Magnetic resonance imaging (MRI) brain abnormalities have been reported in the corpus callosum (CC) of patients with adult-onset hypothyroidism. However, no study has directly compared CC-specific morphological or functional alterations among subclinical hypothyroidism (SCH), overt hypothyroidism (OH), and healthy controls (HC). Moreover, the association of CC alterations with cognition and emotion is not well understood.
METHODS
Demographic data, clinical variables, neuropsychological scores, and MRI data of 152 participants (60 SCH, 37 OH, and 55 HC) were collected. This study investigated the clinical performance, morphological and functional changes of CC subregions across three groups. Moreover, a correlation analysis was performed to explore potential relationships between these factors.
RESULTS
Compared to HC, SCH and OH groups exhibited lower cognitive scores and higher depressive/anxious scores. Notably, rostrum and rostral body volume of CC was larger in the SCH group. Functional connectivity between rostral body, anterior midbody and the right precentral and dorsolateral superior frontal gyrus were increased in the SCH group. In contrast, the SCH and OH groups exhibited a decline in functional connectivity between splenium and the right angular gyrus. Within the SCH group, rostrum volume demonstrated a negative correlation with Montreal Cognitive Assessment and visuospatial/executive scores, while displaying a positive correlation with 24-item Hamilton Depression Rating Scale scores. In the OH group, rostral body volume exhibited a negative correlation with serum thyroid stimulating hormone levels, while a positive correlation with serum total thyroxine and free thyroxine levels.
CONCLUSIONS
This study suggests that patients with different stages of adult-onset hypothyroidism may exhibit different patterns of CC abnormalities. These findings offer new insights into the neuropathophysiological mechanisms in hypothyroidism.
PubMed: 38964705
DOI: 10.1016/j.brainres.2024.149110 -
Brain Research Jul 2024Language aptitude has recently regained interest in cognitive neuroscience. Traditional language aptitude testing included phonemic coding ability, associative memory,...
Language aptitude has recently regained interest in cognitive neuroscience. Traditional language aptitude testing included phonemic coding ability, associative memory, grammatical sensitivity and inductive language learning. Moreover, domain-general cognitive abilities are associated with individual differences in language aptitude, together with factors that have yet to be elucidated. Beyond domain-general cognition, it is also likely that aptitude and experience in domain-specific but non-linguistic fields (e.g. music or numerical processing) influence and are influenced by language aptitude. We investigated some of these relationships in a sample of 152 participants, using exploratory graph analysis, across different levels of regularisation, i.e. sensitivity. We carried out a meta cluster analysis in a second step to identify variables that are robustly grouped together. We discuss the data, as well as their meta-network groupings, at a baseline network sensitivity level, and in two analyses, one including and the other excluding dyslexic readers. Our results show a stable association between language and cognition, and the isolation of multilingual language experience, musicality and literacy. We highlight the necessity of a more comprehensive view of language and of cognition as multivariate systems.
PubMed: 38964704
DOI: 10.1016/j.brainres.2024.149109