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Nature Communications Jun 2024Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods...
Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods rely almost exclusively on bacterial culture from sputum which limits sampling to organisms on the pulmonary surface. Advances in monitoring tuberculous lesions have utilized the common glucoside [F]FDG, yet lack specificity to the causative pathogen Mycobacterium tuberculosis (Mtb) and so do not directly correlate with pathogen viability. Here we show that a close mimic that is also positron-emitting of the non-mammalian Mtb disaccharide trehalose - 2-[F]fluoro-2-deoxytrehalose ([F]FDT) - is a mechanism-based reporter of Mycobacteria-selective enzyme activity in vivo. Use of [F]FDT in the imaging of Mtb in diverse models of disease, including non-human primates, successfully co-opts Mtb-mediated processing of trehalose to allow the specific imaging of TB-associated lesions and to monitor the effects of treatment. A pyrogen-free, direct enzyme-catalyzed process for its radiochemical synthesis allows the ready production of [F]FDT from the most globally-abundant organic F-containing molecule, [F]FDG. The full, pre-clinical validation of both production method and [F]FDT now creates a new, bacterium-selective candidate for clinical evaluation. We anticipate that this distributable technology to generate clinical-grade [F]FDT directly from the widely-available clinical reagent [F]FDG, without need for either custom-made radioisotope generation or specialist chemical methods and/or facilities, could now usher in global, democratized access to a TB-specific PET tracer.
Topics: Animals; Mycobacterium tuberculosis; Positron-Emission Tomography; Trehalose; Tuberculosis; Humans; Mice; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Radiopharmaceuticals; Disease Models, Animal; Female
PubMed: 38937448
DOI: 10.1038/s41467-024-48691-6 -
Journal of Hazardous Materials Jun 2024Plastic-based insulation materials have been widely employed owing to their exceptional durability, cost-effectiveness, low weight, and low thermal conductivity....
Plastic-based insulation materials have been widely employed owing to their exceptional durability, cost-effectiveness, low weight, and low thermal conductivity. Nevertheless, the disposal of the insulation material waste (IMW) within construction waste and its recycling and recovery are challenging. Meanwhile, landfilling or incineration methods can release toxic chemicals into the environment. Consequently, the accumulation of IMW in construction waste has become a pressing environmental concern. To address this issue, this paper proposes a pyrolysis platform as a disposal management method for IMW that employs CO as a reactive medium. IMW composed of polystyrene in the form of extruded polystyrene underwent pyrolysis to yield pyrogenic products containing toxic chemicals. These toxic chemicals were subsequently transformed into syngas via homogeneous reactions with CO under certain thermal conditions and Ni/AlO catalyst. This resulted in a significant reduction in the total peak areas of toxic substances in the pyrogenic oil compared with that obtained using N as a medium. Furthermore, the efficacy of CO was demonstrated to increase with an increase in the atmospheric concentration. This study implied that catalytic pyrolysis under CO conditions is a potential platform for converting toxic chemicals from IMW into syngas through homogeneous reactions with CO.
PubMed: 38909465
DOI: 10.1016/j.jhazmat.2024.134916 -
Environmental Science & Technology Jun 2024The frequency and intensity of global wildfires are escalating, leading to an increase in derived pyrogenic dissolved organic matter (pyDOM), which potentially...
The frequency and intensity of global wildfires are escalating, leading to an increase in derived pyrogenic dissolved organic matter (pyDOM), which potentially influences the riverine carbon reservoir and poses risks to drinking water safety. However, changes in pyDOM properties as it traverses through soil to water bodies are highly understudied due to the challenges of simulating such processes under laboratory conditions. In this study, we extracted soil DOM along hillslope gradients and soil depths in both burned and unburned catchments post wildfire. Using high-resolution mass spectrometry and a substrate-explicit model, we observed significant increases in the relative abundance of condensed aromatics (ConAC) and tannins in wildfire-affected soil DOM. Wildfire-affected soil DOM also displayed a broader spectrum of molecular and thermodynamic properties, indicative of its diverse composition and reactivity. Furthermore, as the fire-induced weakening of topsoil microbial reprocessing abilities hindered the transformation of plant-derived DOM, the relative abundance of lignin-like compounds increased with soil depth in the fire regions. Meanwhile, the distribution of shared molecular formulas along the hillslope gradient (from shoulder to toeslope) exhibited analogous patterns in both burned and unburned catchments. Although there was an increased prevalence of ConAC and tannin in the burned catchments, the relative abundance of these fractions diminished along the hillslope in all three catchments. Based on the substrate-explicit model, the biodegradability exhibited by wildfire-affected DOM fractions offers the possibility of its conversion along hillslopes. Our findings reveal the spatial distribution of DOM properties after a wildfire, facilitating accurate evaluation of dissolved organic carbon composition involved in the watershed-scale carbon cycle.
PubMed: 38904350
DOI: 10.1021/acs.est.3c11056 -
Stem Cell Research & Therapy Jun 2024There is a significant demand for intermediate-scale bioreactors in academic and industrial institutions to produce cells for various applications in drug screening...
BACKGROUND
There is a significant demand for intermediate-scale bioreactors in academic and industrial institutions to produce cells for various applications in drug screening and/or cell therapy. However, the application of these bioreactors in cultivating hiPSC-derived immune cells and other blood cells is noticeably lacking. To address this gap, we have developed a xeno-free and chemically defined intermediate-scale bioreactor platform, which allows for the generation of standardized human iPSC-derived hematopoietic organoids and subsequent continuous production of macrophages (iPSC-Mac).
METHODS
We describe a novel method for intermediate-scale immune cell manufacturing, specifically the continuous production of functionally and phenotypically relevant macrophages that are harvested on weekly basis for multiple weeks.
RESULTS
The continuous production of standardized human iPSC-derived macrophages (iPSC-Mac) from 3D hematopoietic organoids also termed hemanoids, is demonstrated. The hemanoids exhibit successive stage-specific embryonic development, recapitulating embryonic hematopoiesis. iPSC-Mac were efficiently and continuously produced from three different iPSC lines and exhibited a consistent and reproducible phenotype, as well as classical functionality and the ability to adapt towards pro- and anti-inflammatory activation stages. Single-cell transcriptomic analysis revealed high macrophage purity. Additionally, we show the ability to use the produced iPSC-Mac as a model for testing immunomodulatory drugs, exemplified by dexamethasone.
CONCLUSIONS
The novel method demonstrates an easy-to-use intermediate-scale bioreactor platform that produces prime macrophages from human iPSCs. These macrophages are functionally active and require no downstream maturation steps, rendering them highly desirable for both therapeutic and non-therapeutic applications.
Topics: Humans; Induced Pluripotent Stem Cells; Macrophages; Bioreactors; Organoids; Cell Differentiation; Cell Culture Techniques; Hematopoiesis
PubMed: 38886860
DOI: 10.1186/s13287-024-03785-2 -
Environmental Science & Technology Jun 2024
PubMed: 38869366
DOI: 10.1021/acs.est.4c05412 -
Acta Physiologica (Oxford, England) Jun 2024Animals exhibit physiological changes designed to eliminate the perceived danger, provoking similar symptoms of fever. However, a high-grade fever indicates poor...
AIM
Animals exhibit physiological changes designed to eliminate the perceived danger, provoking similar symptoms of fever. However, a high-grade fever indicates poor clinical outcomes. Caspase11 (Casp11) is involved in many inflammatory diseases. Whether Casp11 leads to fever remains unclear. In this study, we investigate the role of the preoptic area of the hypothalamus (PO/AH) microglia Casp11 in fever.
METHODS
We perform experiments using a rat model of LPS-induced fever. We measure body temperature and explore the functions of peripheral macrophages and PO/AH microglia in fever signaling by ELISA, immunohistochemistry, immunofluorescence, flow cytometry, macrophage depletion, protein blotting, and RNA-seq. Then, the effects of macrophages on microglia in a hyperthermic environment are observed in vitro. Finally, adeno-associated viruses are used to knockdown or overexpress microglia Casp11 in PO/AH to determine the role of Casp11 in fever.
RESULTS
We find peripheral macrophages and PO/AH microglia play important roles in the process of fever, which is proved by macrophage and microglia depletion. By RNA-seq analysis, we find Casp11 expression in PO/AH is significantly increased during fever. Co-culture and conditioned-culture simulate the induction of microglia Casp11 activation by macrophages in a non-contact manner. Microglia Casp11 knockdown decreases body temperature, pyrogenic factors, and inflammasome, and vice versa.
CONCLUSION
We report that Casp11 drives fever. Mechanistically, peripheral macrophages transmit immune signals via cytokines to microglia in PO/AH, which activate the Casp11 non-canonical inflammasome. Our findings identify a novel player, the microglia Casp11, in the control of fever, providing an explanation for the transmission and amplification of fever immune signaling.
PubMed: 38864370
DOI: 10.1111/apha.14187 -
Environmental Science & Technology Jun 2024Groundwater contamination by 1,2,3-trichloropropane (TCP) poses a unique challenge due to its human toxicity and recalcitrance to degradation. Previous work suggests...
Role of Nitrogenous Functional Group Identity in Accelerating 1,2,3-Trichloropropane Degradation by Pyrogenic Carbonaceous Matter (PCM) and Sulfide Using PCM-like Polymers.
Groundwater contamination by 1,2,3-trichloropropane (TCP) poses a unique challenge due to its human toxicity and recalcitrance to degradation. Previous work suggests that nitrogenous functional groups of pyrogenic carbonaceous matter (PCM), such as biochar, are important in accelerating contaminant dechlorination by sulfide. However, the reaction mechanism is unclear due, in part, to PCM's structural complexity. Herein, PCM-like polymers (PLPs) with controlled placement of nitrogenous functional groups [i.e., quaternary ammonium (QA), pyridine, and pyridinium cations (py)] were employed as model systems to investigate PCM-enhanced TCP degradation by sulfide. Our results suggest that both PLP-QA and PLP-py were highly effective in facilitating TCP dechlorination by sulfide with half-lives of 16.91 ± 1.17 and 0.98 ± 0.15 days, respectively, and the reactivity increased with surface nitrogenous group density. A two-step process was proposed for TCP dechlorination, which is initiated by reductive ß-elimination, followed by nucleophilic substitution by surface-bound sulfur nucleophiles. The TCP degradation kinetics were not significantly affected by cocontaminants (i.e., 1,1,1-trichloroethane or trichloroethylene), but were slowed by natural organic matter. Our results show that PLPs containing certain nitrogen functional groups can facilitate the rapid and complete degradation of TCP by sulfide, suggesting that similarly functionalized PCM might form the basis for a novel process for the remediation of TCP-contaminated groundwater.
Topics: Sulfides; Polymers; Groundwater; Water Pollutants, Chemical; Carbon; Propane
PubMed: 38848107
DOI: 10.1021/acs.est.3c11010 -
Acta Tropica Jun 2024Phlebotomine sand flies are critical vectors of Leishmania parasites, impacting public health significantly. This study focused on assessing the diversity of sand flies...
Phlebotomine sand flies are critical vectors of Leishmania parasites, impacting public health significantly. This study focused on assessing the diversity of sand flies in a rural area of El Carmen de Bolívar Municipality, northern Colombia, employing rarefaction curves and Hill numbers to understand potential vector communities and inform environmental management. From January 2018 to April 2019 (five samplings), sand flies were collected using CDC light traps with blue LED in domestic/peridomestic/sylvatic ecotopes, identifying species per Young and Duncan (1994) and Galati (2003). Hill numbers provided diversity estimates across samples, while Principal Component Analysis correlated with environmental factors with phlebotomine species presence and abundance. 8,784 phlebotomine individuals were collected; 56.4 % females and 43.6% males (ratio 3:2). These individuals belonged to eight species: Pintomyia evansi, Psychodopygus panamensis, Lutzomyia gomezi, Micropygomyia cayennensis, Evandromyia dubitans, Psathyromyia aclydifera, Pintomyia serrana, and Pintomyia rangeliana; with Pi. evansi being the most abundant species (74.39 %; 6,530 exemplars). The ANOVA showed no significant differences between phlebotomine sand flies abundances across ecotopes (p = 0.018). Species of epidemiological relevance as Pi. evansi and Lu. gomezi not show a positive correlation with environmental variables evaluated, only Ps. panamensis was positively correlated with precipitation. However, the study emphasizes the need for a continuous sand fly monitoring and research to enhance leishmaniasis control strategies, highlighting the necessity to expand knowledge on phlebotomine diversity and environmental interactions to understand vector ecology and disease dynamics better.
PubMed: 38834157
DOI: 10.1016/j.actatropica.2024.107273 -
The Science of the Total Environment Aug 2024Organic soil amendments have been widely adopted to enhance soil organic carbon (SOC) stocks in agroforestry ecosystems. However, the contrasting impacts of pyrogenic...
Organic soil amendments have been widely adopted to enhance soil organic carbon (SOC) stocks in agroforestry ecosystems. However, the contrasting impacts of pyrogenic and fresh organic matter on native SOC mineralization and the underlying mechanisms mediating those processes remain poorly understood. Here, an 80-day experiment was conducted to compare the effects of maize straw and its derived biochar on native SOC mineralization within a Moso bamboo (Phyllostachys edulis) forest soil. The quantity and quality of SOC, the expression of microbial functional genes concerning soil C cycling, and the activity of associated enzymes were determined. Maize straw enhanced while its biochar decreased the emissions of native SOC-derived CO. The addition of maize straw (cf. control) enhanced the O-alkyl C proportion, activities of β-glucosidase (BG), cellobiohydrolase (CBH) and dehydrogenase (DH), and abundances of GH48 and cbhI genes, while lowered aromatic C proportion, RubisCO enzyme activity, and cbbL abundance; the application of biochar induced the opposite effects. In all treatments, the cumulative native SOC-derived CO efflux increased with enhanced O-alkyl C proportion, activities of BG, CBH, and DH, and abundances of GH48 and cbhI genes, and with decreases in aromatic C, RubisCO enzyme activity and cbbL gene abundance. The enhanced emissions of native SOC-derived CO by the maize straw were associated with a higher O-alkyl C proportion, activities of BG and CBH, and abundance of GH48 and cbhI genes, as well as a lower aromatic C proportion and cbbL gene abundance, while biochar induced the opposite effects. We concluded that maize straw induced positive priming, while its biochar induced negative priming within a subtropical forest soil, due to the contrasting microbial responses resulted from changes in SOC speciation and compositions. Our findings highlight that biochar application is an effective approach for enhancing soil C stocks in subtropical forests.
Topics: Zea mays; Charcoal; Soil; Forests; Carbon; Soil Microbiology
PubMed: 38823704
DOI: 10.1016/j.scitotenv.2024.173606 -
Global Change Biology Jun 2024Wildfires directly emit 2.1 Pg carbon (C) to the atmosphere annually. The net effect of wildfires on the C cycle, however, involves many interacting source and sink...
Wildfires directly emit 2.1 Pg carbon (C) to the atmosphere annually. The net effect of wildfires on the C cycle, however, involves many interacting source and sink processes beyond these emissions from combustion. Among those, the role of post-fire enhanced soil organic carbon (SOC) erosion as a C sink mechanism remains essentially unquantified. Wildfires can greatly enhance soil erosion due to the loss of protective vegetation cover and changes to soil structure and wettability. Post-fire SOC erosion acts as a C sink when off-site burial and stabilization of C eroded after a fire, together with the on-site recovery of SOC content, exceed the C losses during its post-fire transport. Here we synthesize published data on post-fire SOC erosion and evaluate its overall potential to act as longer-term C sink. To explore its quantitative importance, we also model its magnitude at continental scale using the 2017 wildfire season in Europe. Our estimations show that the C sink ability of SOC water erosion during the first post-fire year could account for around 13% of the C emissions produced by wildland fires. This indicates that post-fire SOC erosion is a quantitatively important process in the overall C balance of fires and highlights the need for more field data to further validate this initial assessment.
Topics: Wildfires; Carbon Cycle; Soil Erosion; Carbon; Europe; Soil; Carbon Sequestration; Fires; Models, Theoretical
PubMed: 38822629
DOI: 10.1111/gcb.17354