ABSTRACT
The role and mechanisms of DEP exposure on thyroid injury are not yet clear. This study explores thyroid damage induced by in vivo DEP exposure using a mouse model. This study has observed alterations in thyroid follicular architecture, including rupture, colloid overflow, and the formation of voids. Additionally, there was a significant decrease in the expression levels of proteins involved in thyroid hormone synthesis, such as thyroid peroxidase and thyroglobulin, their trend of change is consistent with the damage to the thyroid structure. Serum levels of triiodothyronine and tetraiodothyronine were raise. However, the decrease in TSH expression suggests that the function of the HPT axis is unaffected. To delve deeper into the intrinsic mechanisms of thyroid injury, we performed KEGG pathway enrichment analysis, which revealed notable alterations in the cell adhesion signaling pathway. Our immunofluorescence results show that DEP exposure impairs thyroid adhesion, and integrin α3ß1 plays an important role. CD151 binds to α3ß1, promoting multimolecular complex formation and activating adhesion-dependent small GTPases. Our in vitro model has confirmed the pivotal role of integrin α3ß1 in thyroid cell adhesion, which may be mediated by the CD151/α3ß1/Rac1 pathway. In summary, exposure to DEP disrupts the structure and function of the thyroid, a process that likely involves the regulation of cell adhesion through the CD151/α3ß1/Rac1 pathway, leading to glandular damage.
Subject(s)
Integrin alpha3beta1 , Thyroid Gland , Vehicle Emissions , Animals , Mice , Thyroid Gland/drug effects , Vehicle Emissions/toxicity , Integrin alpha3beta1/metabolism , Cell Adhesion/drug effects , Air Pollutants/toxicity , Particulate Matter/toxicity , Thyroid Epithelial Cells/drug effects , Thyroid Epithelial Cells/metabolism , Signal TransductionABSTRACT
The Baeyer-Villiger oxidation of ketones is a crucial oxygen atom transfer (OAT) process used for ester production. Traditionally, Baeyer-Villiger oxidation is accomplished by thermally oxidizing the OAT from stoichiometric peroxides, which are often difficult to handle. Electrochemical methods hold promise for breaking the limitation of using water as the oxygen atom source. Nevertheless, existing demonstrations of electrochemical Baeyer-Villiger oxidation face the challenges of low selectivity. We report in this study a strategy to overcome this challenge. By employing a well-known water oxidation catalyst, Fe2O3, we achieved nearly perfect selectivity for the electrochemical Baeyer-Villiger oxidation of cyclohexanone. Mechanistic studies suggest that it is essential to produce surface hydroperoxo intermediates (M-OOH, where M represents a metal center) that promote the nucleophilic attack on ketone substrates. By confining the reactions to the catalyst surfaces, competing reactions (e.g., dehydrogenation, carboxylic acid cation rearrangements, and hydroxylation) are greatly limited, thereby offering high selectivity. The surface-initiated nature of the reaction is confirmed by kinetic studies and spectroelectrochemical characterizations. This discovery adds nucleophilic oxidation to the toolbox of electrochemical organic synthesis.
ABSTRACT
Airway epithelium is extraordinary vulnerable to damage owning to continuous environment exposure. Subsequent repair is therefore essential to restore the homeostasis of respiratory system. Disruptions in respiratory epithelial repair caused by nanoparticles exposure have been linked to various human diseases, yet implications in repair process remain incompletely elucidated. This study aims to elucidate the key stage in epithelial repair disturbed by carbon black (CB) nanoparticles, highlighting the pivotal role of ΔNp63 in mediating the epithelium repair. A competitive-like binding between CB and beta-catenin 1 (CTNNB1) to ΔNp63 is proposed to elaborate the underlying toxicity mechanism. Specifically, CB exhibits a remarkable inhibitory effect on cell proliferation, leading to aberrant airway epithelial repair, as validated in air-liquid culture. ΔNp63 drives efficient epithelial proliferation during CB exposure, and CTNNB1 was identified as a target of ΔNp63 by bioinformatics analysis. Further molecular dynamics simulation reveals that oxygen-containing functional groups on CB disrupt the native interaction of CTNNB1 with ΔNp63 through competitive-like binding pattern. This process modulates CTNNB1 expression, ultimately restraining proliferation during respiratory epithelial repair. Overall, the current study elucidates that the diminished interaction between CTNNB1 and ΔNp63 impedes respiratory epithelial repair in response to CB exposure, thereby enriching the public health risk assessment on CB-related respiratory diseases.
Subject(s)
Soot , beta Catenin , Soot/toxicity , beta Catenin/metabolism , Humans , Respiratory Mucosa , Transcription Factors/metabolism , Tumor Suppressor Proteins/metabolism , Cell Proliferation , Epithelial Cells , Nanoparticles/toxicityABSTRACT
Halogenated organic compounds (HOCs) are a class of contaminants showing high toxicity, low biodegradability, and high bioaccumulation potential, especially chlorinated and brominated HOCs (Cl/Br-HOCs). Knowledge gaps exist on whether novel Cl/Br-HOCs could penetrate the placental barrier and cause adverse birth outcomes. Herein, 326 cord blood samples were collected in a hospital in Jinan, Shandong Province from February 2017 to January 2022, and 44 Cl/Br-HOCs were identified with communicating confidence level above 4 based on a nontarget approach, covering veterinary drugs, pesticides, and their transformation products, pharmaceutical and personal care products, disinfection byproducts, and so on. To our knowledge, the presence of closantel, bromoxynil, 4-hydroxy-2,5,6-trichloroisophthalonitrile, 2,6-dibromo-4-nitrophenol, and related components in cord blood samples was reported for the first time. Both multiple linear regression (MLR) and Bayesian kernel machine regression (BKMR) models were applied to evaluate the relationships of newborn birth outcomes (birth weight, length, and ponderal index) with individual Cl/Br-HOC and Cl/Br-HOCs mixture exposure, respectively. A significantly negative association was observed between pentachlorophenol exposure and newborn birth length, but the significance vanished after the false discovery rate correction. The BKMR analysis showed that Cl/Br-HOCs mixture exposure was significantly associated with reduced newborn birth length, indicating higher risks of fetal growth restriction. Our findings offer an overview of Cl/Br-HOCs exposome during the early life stage and enhance the understanding of its exposure risks.
ABSTRACT
Molecular Ir catalysts have emerged as an important class of model catalysts for understanding structure-activity relationships in water oxidation, a reaction that is central to renewable fuel synthesis. Prior efforts have mostly focused on controlling and elucidating the emergence of active species from prepared precursors. However, the development of efficient and stable molecular Ir catalysts also necessitates probing of reaction intermediates. To date, relatively little is known about the key intermediates in the cycles of the molecular Ir catalysts. Herein, we probed the catalytic cycle of a homogeneous Ir catalyst ("blue dimer") at a Au electrode/aqueous electrolyte interface by combining surface-enhanced infrared absorption spectroscopy (SEIRAS) with phase-sensitive detection (PSD). Cyclic voltammograms (CVs) from 1.4 to 1.7 VRHE (RHE = reversible hydrogen electrode) give rise to a band at â¼818 cm-1, whereas CVs from 1.4 to ≥1.85 VRHE generate an additional band at â¼1146 cm-1. Isotope labeling experiments indicate that the bands at â¼818 and â¼1146 cm-1 are attributable to oxo (IrVâO) and superoxo (IrIV-OOâ¢) moieties, respectively. This study establishes PSD-SEIRAS as a sensitive tool for probing water oxidation cycles at electrode/electrolyte interfaces and demonstrates that the relative abundance of two key intermediates can be tuned by the thermodynamic driving force of the reaction.
ABSTRACT
Phosphatidylethanolamine binding protein (PEBP) plays an important role in regulating flowering time and morphogenesis of plants. However, the identification and functional analysis of PEBP gene in pineapple (AcPEBP) have not been systematically studied. The pineapple genome contained 11 PEBP family members, which were subsequently classified into three subfamilies (FT-like, TFL-like and MFT-like) based on phylogenetic relationships. The arrangement of these 11 shows an unequal pattern across the six chromosomes of pineapple the pineapple genome. The anticipated outcomes of the promoter cis-acting elements indicate that the PEBP gene is subject to regulation by diverse light signals and endogenous hormones such as ethylene. The findings from transcriptome examination and quantitative real-time polymerase chain reaction (qRT-PCR) indicate that FT-like members AcFT3 and AcFT4 display a heightened expression level, specifically within the floral structures. The expression of AcFT3 and AcFT4 increases sharply and remains at a high level after 4 days of ethylene induction, while the expression of AcFT7 and AcMFT1 decreases gradually during the flowering process. Additionally, AcFT3, AcFT4 and AcFT7 show specific expression in different floral organs of pineapple. These outcomes imply that members belonging to the FT-like subfamily may have a significant impact on the process of bud differentiation and flower development. Through transcriptional activation analysis, it was determined that AcFT4 possesses transcriptional activation capability and is situated in the nucleus and peripheral cytoplasm. Overexpression of AcFT4 in Arabidopsis resulted in the promotion of early flowering by 6-7 days. The protein interaction prediction network identified potential flower regulators, including CO, AP1, LFY and SOC1, that may interact with PEBP proteins. This study explores flower development in pineapple, thereby serving as a valuable reference for future research endeavors in this domain.
ABSTRACT
Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli) has been identified in various water environments, posing a serious risk to public health. However, whether and how ESBL-producing genes in water-derived E. coli can spread among mammalian gut microbiota via drinking water is largely unclear. To address this problem, horizontal transfer characterization of ESBL-producing genes in mice gut microbiota was determined after the oral ingestion of contaminated water by ESBL-producing E. coli, and then the driving factors were comprehensively examined from multiple different perspectives. The results showed that water-borne ESBL-producing E. coli can colonize in the mice intestine, the ESBL-producing genes can horizontally spread among gut microbiota, and the recipient bacteria include opportunistic pathogens Klebsiella pneumoniae and Salmonella enterica. This horizontal spread may be attributed to the intestinal micro-environment changes caused by the ingestion of contaminated water by ESBL-producing E. coli. These changes, including gut microbiota diversity, increased levels of inflammatory response and reactive oxygen species, cell membrane permeability, and expression levels of conjugative transfer-related genes, are all major driving factors for horizontal transfer of ESBL-producing genes in mice gut microbiota. Our findings highlight the potential for ESBL-producing E. coli to spread resistance genes to mammalian gut microbiota during ingestion of contaminated water.
Subject(s)
Escherichia coli Infections , Klebsiella Infections , Animals , Mice , Escherichia coli/genetics , Escherichia coli/metabolism , Escherichia coli Infections/microbiology , Anti-Bacterial Agents , beta-Lactamases/genetics , Klebsiella Infections/microbiology , Eating , MammalsABSTRACT
Heterogeneous water oxidation catalysis is central to the development of renewable energy technologies. Recent research has suggested that the reaction mechanisms are sensitive to the hole density at the active sites. However, these previous results were obtained on catalysts of different materials featuring distinct active sites, making it difficult to discriminate between competing explanations. Here, a comparison study based on heterogenized dinuclear Ir catalysts (Ir-DHC), which feature the same type of active site on different supports, is reported. The prototypical reaction was water oxidation triggered by pulsed irradiation of suspensions containing a light sensitizer, Ru(bpy)32+, and a sacrificial electron scavenger, S2O82-. It was found that at relatively low temperatures (288-298 K), the water oxidation activities of Ir-DHC on indium tin oxide (ITO) and CeO2 supports were comparable within the studied range of fluences (62-151 mW cm-2). By contrast, at higher temperatures (310-323 K), Ir-DHC on ITO exhibited a ca. 100% higher water oxidation activity than on CeO2. The divergent activities were attributed to the distinct abilities of the supporting substrates in redistributing holes. The differences were only apparent at relatively high temperatures when hole redistribution to the active site became a limiting factor. These findings highlight the critical role of the supporting substrate in determining the turnover at active sites of heterogeneous catalysts.
ABSTRACT
Atomically dispersed catalysts such as single-atom catalysts have been shown to be effective in selectively oxidizing methane, promising a direct synthetic route to value-added oxygenates such as acetic acid or methanol. However, an important challenge of this approach has been that the loading of active sites by single-atom catalysts is low, leading to a low overall yield of the products. Here, we report an approach that can address this issue. It utilizes a metal-organic framework built with porphyrin as the linker, which provides high concentrations of binding sites to support atomically dispersed rhodium. It is shown that up to 5 wt% rhodium loading can be achieved with excellent dispersity. When used for acetic acid synthesis by methane oxidation, a new benchmark performance of 23.62 mmol·gcat-1·h-1 was measured. Furthermore, the catalyst exhibits a unique sensitivity to light, producing acetic acid (under illumination, up to 66.4% selectivity) or methanol (in the dark, up to 65.0% selectivity) under otherwise identical reaction conditions.
ABSTRACT
Direct synthesis of CH3 COOH from CH4 and CO2 is an appealing approach for the utilization of two potent greenhouse gases that are notoriously difficult to activate. In this Communication, we report an integrated route to enable this reaction. Recognizing the thermodynamic stability of CO2 , our strategy sought to first activate CO2 to produce CO (through electrochemical CO2 reduction) and O2 (through water oxidation), followed by oxidative CH4 carbonylation catalyzed by Rh single atom catalysts supported on zeolite. The net result was CH4 carboxylation with 100 % atom economy. CH3 COOH was obtained at a high selectivity (>80 %) and good yield (ca. 3.2â mmol g-1 cat in 3â h). Isotope labelling experiments confirmed that CH3 COOH is produced through the coupling of CH4 and CO2 . This work represents the first successful integration of CO/O2 production with oxidative carbonylation reaction. The result is expected to inspire more carboxylation reactions utilizing preactivated CO2 that take advantage of both products from the reduction and oxidation processes, thus achieving high atom efficiency in the synthesis.
ABSTRACT
Triclosan (TCS) is an antiseptic incorporated in consumer goods and personal care products that can be absorbed via the skin, raising public health concerns for its continuous detection in human biofluids and tissues. Epidemiology has associated TCS exposure with thyroid function disturbances and decreasing serum thyroid hormone (TH) levels, but the underlying mechanism remains unclear. In this study, we revealed hypothyroidism and histological alternation in the thyroid of mice with chronic percutaneous exposure to TCS, indicating a TCS-caused thyroid impairment. Subsequently, multi-omics approaches were performed to investigate the molecular mechanism of the thyroid in response to long-term dermal TCS exposure. We discovered that TCS interfered with the TH synthesis as indicated by the changes in the levels of the synthetic materials for TH (iodide, Tg, and H2O2) and affected TH release by the downregulation of lysosomal enzymes. The upregulation of glycolysis, tricarboxylic acid cycle, fatty acid, amino acid metabolism, and adenine salvage in the thyroid was also observed after TCS exposure. All these changes led to the elevation of ATP, serving as a rescue for the decreasing thyroid functions. Together, our study demonstrated TCS-induced thyroid damage and identified the interrupted pathways, providing meaningful insight into the molecular mechanisms underpinning the potential health influence of TCS in humans.
Subject(s)
Anti-Infective Agents, Local , Thyroid Gland , Triclosan , Animals , Humans , Mice , Anti-Infective Agents, Local/toxicity , Hydrogen Peroxide , Proteomics , Thyroid Hormones , Triclosan/toxicityABSTRACT
Triclosan (TCS) is a widespread antimicrobial agent that is associated with many adverse health outcomes. Its gut toxicity has been attributed to the molecular modifications mediated by commensal microbes, but microbial transformations of TCS derivatives in the gut lumen are still largely unknown. Aromatic hydroxylation is the predominant oxidative metabolism of TCS that linked to its toxicological effects in host tissues. Here, we aimed to reveal the biological fates of hydroxyl-TCS (OH-TCS) in the colon, where intestinal microbes mainly reside. Unlike the profiles generated via host metabolism, OH-TCS species remain unconjugated in human stools from a cohort study. Through tracking molecular compositions in mouse intestinal tract, elevated abundance of free-form OH-TCS while reduced abundance of conjugated forms was observed in the colon digesta and mucosa. Using antibiotic-treated and germ-free mice, as well as in vitro approaches, we demonstrate that gut microbiota-encoded enzymes efficiently convert glucuronide/sulfate-conjugated OH-TCS, which are generated from host metabolism, back to their bioactive free-forms in colon tissues. Thus, host-gut microbiota metabolic interactions of TCS derivatives were proposed. These results shed light on the crucial roles of microbial metabolism in TCS toxicity, and highlight the importance of incorporating gut microbial transformations in health risk assessment of environmental chemicals.
Subject(s)
Gastrointestinal Microbiome , Triclosan , Mice , Humans , Animals , Triclosan/metabolism , Cohort Studies , Colon , Oxidative StressABSTRACT
Glyphosate (GLY) exposure has been reported to damage organs in animals, in particular the liver, due to increased reactive oxygen species (ROS). Ferroptosis is defined as a new type of cell death that is characterized by the increase of ROS. The purpose of this study was to elucidate whether the relationship between ferroptosis and GLY-induced hepatotoxicity is of significance to enlarge the knowledge about GLY toxicity and consequences for human and animal health. To this end, in this study, we investigated the role of ferroptosis in GLY-induced hepatotoxicity both in vivo and in vitro. The results showed that GLY exposure triggered ferroptosis in L02 cells, but pretreatment with ferroptosis inhibitor ferrostatin (Fer-1) rescued ferroptosis-induced injury, thereby indicating that ferroptosis plays a key role in GLY-induced hepatotoxicity. Moreover, N-acetylcysteine, a glutathione (GSH) synthesis precursor, reversed GLY-triggered ferroptosis damage, thus indicating that GSH exhaustion may be a prerequisite for GLY-triggered hepatotoxicity. Mechanistically, GLY inhibited GSH biosynthesis via blocking the phosphorylation and nuclear translocation of Nrf2, which resulted in GSH depletion-induced hepatocyte ferroptosis. In a mouse model, GLY exposure triggered ferroptosis-induced liver damage, which can be rescued by pretreatment with Fer-1 or tBHQ (a specific agonist of Nrf2). To our knowledge, this is the first study to reveal that GLY-triggered hepatocyte ferroptosis via suppressing Nrf2/GSH/GPX4 axis exacerbates hepatotoxicity, which expands our knowledge about GLY toxicity in animal and human health.
Subject(s)
Chemical and Drug Induced Liver Injury , Ferroptosis , Animals , Humans , Mice , Chemical and Drug Induced Liver Injury/etiology , Glutathione , Hepatocytes/metabolism , NF-E2-Related Factor 2 , Reactive Oxygen Species , Glycine/analogs & derivatives , Glycine/pharmacology , Glycine/toxicity , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , GlyphosateABSTRACT
Flowering is an important factor to ensure the success of plant reproduction, and reasonable flowering time is crucial to the crop yield. BBX transcription factors can regulate several growth and development processes. However, there is little research on whether BBX is involved in flower formation and floral organ development of pineapple. In this study, AcBBX5, a BBX family gene with two conserved B-box domains, was identified from pineapple. Subcellular localization analysis showed that AcBBX5 was located in the nucleus. Transactivation analysis indicated that AcBBX5 had no significant toxic effects on the yeast system and presented transcriptional activation activity in yeast. Overexpression of AcBBX5 delayed flowering time and enlarged flower morphology in Arabidopsis. Meanwhile, the expression levels of AtFT, AtSOC1, AtFUL and AtSEP3 were decreased, and the transcription levels of AtFLC and AtSVP were increased in AcBBX5-overexpressing Arabidopsis, which might lead to delayed flowering of transgenic plants. Furthermore, transcriptome data and QRT-PCR results showed that AcBBX5 was expressed in all floral organs, with the high expression levels in stamens, ovaries and petals. Yeast one-hybrid and dual luciferase assay results showed that AcBBX5 bound to AcFT promoter and inhibited AcFT gene expression. In conclusion, AcBBX5 was involved in flower bud differentiation and floral organ development, which provides an important reference for studying the functions of BBX and the molecular regulation of flower.
ABSTRACT
OBJECTIVE: Endometrial cancer (EC) is the most common invasive gynecological malignancy. This study aimed to retrospectively analyze the relationship between 18F-fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) parameters and clinicopathological factors in EC patients, and assess whether 18F-FDG PET/CT can be applied for predicting the expressed status of histologic molecular markers. METHODS: Pretreatment clinicopathological characteristics and 18F-FDG PET/CT parameters of maximum standard uptake value (SUVmax), metabolic tumor volume and total lesion glycolysis of primary lesion (MTV-P and TLG-P), and combination of primary lesion and metastases (MTV-C and TLG-C) were retrospectively reviewed in 101 patients with EC. RESULTS: The median age of these 101 patients was 55 years (range, 35-85 years), and 95 patients (94.1%) presented with abnormal vaginal bleeding, 26 patients (25.7%) with elevated serum cancer antigen 125 (CA-125) and 46 patients (45.5%) with increased human epididymis protein 4 (HE4). Sixty-nine cases were at International Federation of Gynecology and Obstetrics (FIGO) stage I, eight at stage II, 20 at stage III, and four at stage IV. FDG uptake was avid in all cases, and the median SUVmax, MTV-P, TLG-P, MTV-C, and TLG-C were 12.9 (range, 2.8-34.2), 8.1 (range, 0.9-547.8), 52.2 (range, 2.5-4420.6), 8.2 (range, 0.9-790.3), and 58.4 (range, 2.5-6972.2), respectively. Estrogen receptor (ER) and progesterone receptor (PR) positive expressions were in 93.1% (94/101) and 90.1% (91/101) patients, respectively. The median Ki-67 index of 101 cases was 40% (range, 0-95%). P53 pattern was tested in 89 patients and 24 cases were mutant type (27.0%). Mesenchymal-epithelial transition factor (c-Met) expression was investigated in 86 patients, and the positivity was in 36 patients (41.9%). Higher PET/CT metabolic parameters were observed in patients with elevated CA-125 and HE4, advanced FIGO stage and higher Ki-67 index (P < 0.05), but had no association with ER/PR expression, P53 pattern, and c-Met expression (P > 0.05). CONCLUSION: FDG uptake in EC was associated with serum CA-125 and HE4, FIGO stage, and Ki-67 index, but no correlations were found between glucose metabolism and ER/PR, P53, and c-Met.
Subject(s)
Endometrial Neoplasms , Fluorodeoxyglucose F18 , Female , Humans , Adult , Middle Aged , Aged , Aged, 80 and over , Fluorodeoxyglucose F18/metabolism , Positron Emission Tomography Computed Tomography , Retrospective Studies , Ki-67 Antigen/metabolism , Tumor Suppressor Protein p53/metabolism , Tomography, X-Ray Computed , Tumor Burden , Endometrial Neoplasms/pathology , Glycolysis , Prognosis , RadiopharmaceuticalsABSTRACT
MADS-box genes play crucial roles in plant vegetative and reproductive growth, better development of inflorescences, flower, and fruit. Pineapple is a typical collective fruit, and a comprehensive analysis of the MADS-box gene family in the development of floral organs of pineapple is still lacking. In this study, the whole-genome survey and expression profiling of the MADS-box family in pineapple were introduced. Forty-four AcMADS genes were identified in pineapple, 39 of them were located on 18 chromosomes and five genes were distributed in five scaffolds. Twenty-two AcMADS genes were defined as 15 pairs of segmental duplication events. Most members of the type II subfamily of AcMADS genes had higher expression levels in floral organs compared with type I subfamily, thereby suggesting that AcMADS of type II may play more crucial roles in the development of floral organs of pineapple. Six AcMADS genes have significant tissue-specificity expression, thereby suggesting that they may participate in the formation of one or more floral organs. This study provides valuable insights into the role of MADS-box gene family in the floral organ development of pineapple.
ABSTRACT
Aiming at the problems of low learning efficiency, slow convergence speed, and low prediction accuracy of traditional data-driven model applied to tool cutting force prediction, a prediction method of tool cutting force based on ant lion optimizer (ALO) extreme learning machine (ELM) is proposed. ALO was used to improve the weights of input layer and hidden layer of ELM, so as to improve its prediction accuracy. The tool cutting force prediction models were established by using ALO-ELM, ELM, BP (backpropagation) neural network, and support vector machine, respectively. The experimental results show that the mean square error, mean absolute percentage error, and mean absolute error of ALO-ELM prediction model are 0.9911%, 0.0011%, and 1.0863%, respectively, which are far lower than the other three prediction models. ALO-ELM prediction model has stronger prediction accuracy and generalization ability, which can be effectively applied to the prediction of cutting force.
Subject(s)
Algorithms , Neural Networks, Computer , Support Vector MachineABSTRACT
The application of mass spectrometry imaging (MSI) to explore the responses of cancer cell spheroids (CCS) after treatment of exogenous molecules has attracted growing attention. Increasing studies have utilized MSI to image the two-dimensional distributions of exogenous and endogenous molecules in planar CCS sections. However, because CCS are volumetric and heterogenous, maintaining their three-dimensional (3D) information is essential for acquiring a better understanding of the tumor microenvironment and mechanisms of action of exogenous molecules. Here, an established method of 3D MSI was applied to distinguish the distributions of triclosan sulfate and endogenous lipids in three microregions of colon CCS with an enhanced growth induced by the treatment of triclosan, a common antimicrobial agent. The results of 3D MSI showed that triclosan sulfate gradually accumulated from the periphery to the entire structure of CCS and finally localized in the core region. Spatial lipidomics analysis revealed that the upregulated phosphatidylethanolamine (fold change (FD) = 1.26, p = 0.0021), phosphatidylinositol (FD = 1.17, p = 0.0180), and phosphatidylcholine (FD = 1.22, p = 0.0178) species mainly distributed in the outer proliferative region, while the upregulated sphingomyelin (FD = 1.18, p = 0.024) species tended to distribute in the inner necrotic region. Our results suggest that a competitive mechanism between inhibiting and promoting CCS growth might be responsible for the proliferation of CCS treated with triclosan.
Subject(s)
Colonic Neoplasms , Triclosan , Colonic Neoplasms/drug therapy , Humans , Mass Spectrometry/methods , Phosphatidylcholines , Phosphatidylethanolamines , Phosphatidylinositols , Sphingomyelins , Sulfates , Triclosan/pharmacology , Tumor MicroenvironmentABSTRACT
The COVID-19 pandemic has exerted a huge adverse influence on global teaching activities and students' psychological status. Veterinary microbiology is mainly concerned with bacterial and viral diseases, including coronavirus diseases. An innovative online-to-offline teaching approach for this course was established to stimulate students' learning initiative and mitigate their anxiety about COVID-19. A well-established massive open online course (MOOC) was first adopted as preview material before class, followed by in-person teaching. Additionally, COVID-19-related scientific papers were also used as pre-class reading material in veterinary microbiology and were further explained in class. The effect of this innovative teaching mode was systematically evaluated by final examination scores and questionnaires. The average score (81.75) and excellence score rating (> 85 scores, 37.3%) resulting from this blended teaching mode were not statistically higher than those of the online-only (79.19, p = .115; 28.6%, p = .317) or offline-only (79.47, p = .151; 27.9%, p = .269) teaching modes. This may be due to the sample size investigated; however, the results indicate that the innovative teaching mode did not decrease teaching quality. Additionally, most subjects (72.9%) were satisfied with the blended mode and supported its future use. Intriguingly, the introduction of COVID-19-related scientific papers helped students understand virology, relieve their anxiety, and increase their professional identity. Collectively, the innovative approach to teaching veterinary microbiology in this study provides a beneficial reference for other teachers to maintain and improve teaching quality.
ABSTRACT
Plastic debris in the global biosphere is an increasing concern, and nanoplastic (NPs) toxicity in humans is far from being understood. Studies have indicated that NPs can affect mitochondria, but the underlying mechanisms remain unclear. The liver and lungs have important metabolic functions and are vulnerable to NP exposure. In this study, we investigated the effects of 80 nm NPs on mitochondrial functions and metabolic pathways in normal human hepatic (L02) cells and lung (BEAS-2B) cells. NP exposure did not induce mass cell death; however, transmission electron microscopy analysis showed that the NPs could enter the cells and cause mitochondrial damage, as evidenced by overproduction of mitochondrial reactive oxygen species, alterations in the mitochondrial membrane potential, and suppression of mitochondrial respiration. These alterations were observed at NP concentrations as low as 0.0125 mg/mL, which might be comparable to the environmental levels. Nontarget metabolomics confirmed that the most significantly impacted processes were mitochondrial-related. The metabolic function of L02 cells was more vulnerable to NP exposure than that of BEAS-2B cells, especially at low NP concentrations. This study identifies NP-induced mitochondrial dysfunction and metabolic toxicity pathways in target human cells, providing insight into the possibility of adverse outcomes in human health.