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Earthworms are pivotal in soil ecosystems due to their crucial role in shaping soil characteristics through casts and burrow walls. Previous research has predominantly focused on the direct impact of soil pollution on live earthworms, overlooking the subsequent effects on earthworm-mediated soil, such as casts and burrow walls. Using 2D-terraria as incubation containers and the geophagous earthworm species Metaphire guillelmi, this study assessed the change in various properties of earthworm-mediated soil in both uncontaminated soils and Cd- and Pye-contaminated soils. Overall, both Cd and Pye overall improved the ammonium nitrogen (NH4+-N), Olsen's phosphorus (Olsen-P) levels, and invertase and catalase activities while decreasing catalase activities in earthworm-mediated soil. They also fluctuating affected the pH, soil organic matter (SOM) content, soil urease, alkaline phosphatase activities, and microbial functional genes in the cast and burrow walls. These results indicated that earthworms remained crucial "ecosystem engineers" even in polluted soil. Additionally, differences were observed in the responses of properties between casts and burrow walls, showing unequal contributions of transit-through-gut and burrowing processes to soil modification. Specifically, transit-through-gut was found to have a more significant influence on soil NH4+-N and Olsen-P content compared to burrowing behavior. Regarding the pattern of microbial functional genes in earthworm-associated compartments, results revealed that they differed significantly in casts from those in bulk soil and burrow walls under unpolluted conditions, with pollution-enhancing disparities among compartments. Furthermore, NH4+-N and Olsen-P content, urease, and catalase activities in burrow walls and/or casts were identified as potential biomarkers for soil pollution, exhibiting a clear dose-effect relationship. Developing such biomarkers could address ethical concerns related to conventional earthworm biomarkers that require sacrificing earthworms. This study provides insights into the consequences of soil pollution on earthworm-mediated soil components, highlighting the importance of considering the indirect effects of contaminants on soil ecosystems.
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BACKGROUND: The risk of second tumors after chimeric antigen receptor (CAR) T-cell therapy, especially the risk of T-cell neoplasms related to viral vector integration, is an emerging concern. METHODS: We reviewed our clinical experience with adoptive cellular CAR T-cell therapy at our institution since 2016 and ascertained the occurrence of second tumors. In one case of secondary T-cell lymphoma, a broad array of molecular, genetic, and cellular techniques were used to interrogate the tumor, the CAR T cells, and the normal hematopoietic cells in the patient. RESULTS: A total of 724 patients who had received T-cell therapies at our center were included in the study. A lethal T-cell lymphoma was identified in a patient who had received axicabtagene ciloleucel therapy for diffuse large B-cell lymphoma, and both lymphomas were deeply profiled. Each lymphoma had molecularly distinct immunophenotypes and genomic profiles, but both were positive for Epstein-Barr virus and were associated with DNMT3A and TET2 mutant clonal hematopoiesis. No evidence of oncogenic retroviral integration was found with the use of multiple techniques. CONCLUSIONS: Our results highlight the rarity of second tumors and provide a framework for defining clonal relationships and viral vector monitoring. (Funded by the National Cancer Institute and others.).
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Antineoplásicos Imunológicos , Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Linfoma de Células T , Segunda Neoplasia Primária , Receptores de Antígenos Quiméricos , Feminino , Humanos , Pessoa de Meia-Idade , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Hematopoiese Clonal , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/genética , Imunoterapia Adotiva/efeitos adversos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/terapia , Linfoma de Células T/etiologia , Linfoma de Células T/genética , Linfoma de Células T/imunologia , Linfoma de Células T/terapia , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/etiologia , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Integração ViralRESUMO
Earthworms are considered to be excellent bioindicators of soil pollution. In recent years, there has been increasing interest in examining the effects of soil pollution on earthworm-associated microbiomes, with a particular focus on the gut microbiomes. However, relatively little effort has been invested in comprehensively investigating other microbiomes associated with earthworms and their responses to soil pollution. To fill this gap, we systematically studied the effects of Cd, pyrene, and combined pollution on the bacterial community in different vermicompartments, i.e., burrow wall, gut, and cast, in both epigeic Eisenia fetida and anecic Metaphire guillelmi, using a 2D-terraria incubator and high-throughput sequencing techniques. The results showed that bacterial alpha diversity followed the order of burrow wall > cast > gut, and this did not vary with soil pollution or earthworm ecotypes. Moreover, the dominant phyla in the vermicompartments were similar across different pollution treatments. Principal coordinate analysis (PCoA) revealed that the bacterial communities in different vermicompartments and ecotypes of earthworm were separated from each other, whereas they were grouped together in polluted treatments and unpolluted conditions. These results imply that even in polluted soil, vermicompartment and earthworm ecotypes remain the most significant factors affecting earthworm-associated microbiomes. However, the impacts of soil pollution on the bacterial composition in each vermicompartment were still evident. A comprehensive analysis revealed that the gut bacterial communities are more sensitive to soil contamination than casts and burrow wall in different ecotypes. Additionally, linear discriminant analysis of effect size (LefSe) identified several bacteria in Gemmatimonadota, the Firmicutes phylum in the burrow walls, and Patescibacteria (phyla) in the gut as potential biomarkers for pyrene contamination in soil. This research provides a comprehensive understanding of the effects of soil pollution on earthworm-associated microbiomes, thereby enhancing our understanding of earthworm ecotoxicology and soil pollution management.
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Oligoquetos , Poluentes do Solo , Animais , Oligoquetos/microbiologia , Oligoquetos/fisiologia , Cádmio/toxicidade , Bactérias/genética , Poluição Ambiental , Solo , Poluentes do Solo/análise , Pirenos/farmacologiaRESUMO
Once challenged by the SARS-CoV-2 virus, the human host immune system triggers a dynamic process against infection. We constructed a mathematical model to describe host innate and adaptive immune response to viral challenge. Based on the dynamic properties of viral load and immune response, we classified the resulting dynamics into four modes, reflecting increasing severity of COVID-19 disease. We found the numerical product of immune system's ability to clear the virus and to kill the infected cells, namely immune efficacy, to be predictive of disease severity. We also investigated vaccine-induced protection against SARS-CoV-2 infection. Results suggested that immune efficacy based on memory T cells and neutralizing antibody titers could be used to predict population vaccine protection rates. Finally, we analyzed infection dynamics of SARS-CoV-2 variants within the construct of our mathematical model. Overall, our results provide a systematic framework for understanding the dynamics of host response upon challenge by SARS-CoV-2 infection, and this framework can be used to predict vaccine protection and perform clinical diagnosis.
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COVID-19 , Viroses , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Carga ViralRESUMO
Negative capacitance usually exists in ferroelectric materials, and its instinct nonlinearity and negative capacitance render its potential applications. To date, the single negative capacitance device is commonly unavailable. Hence, it is necessary to build a negative capacitor emulator in hardware for further investigating its electrical characteristics and applications. Based on a simple negative capacitor mathematical model, an emulator circuit that can mimic the S-shaped voltage-charge characteristics of the negative capacitor is proposed. The proposed emulator is composed of commercial off-the-shelf components, such as operational amplifiers, resistors, and capacitors. Based on the negative capacitor, we design a new chaotic circuit that can generate the single-period, double-period, single-scroll chaos, double-scroll chaos, and so on. The theoretical calculation, simulation analysis, and hardware experimental verification manifest that this proposed emulator circuit can be operated as a negative capacitor and applied in the chaotic circuit.
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Efficient separation of oil droplets from oil/water emulsions is necessary for many energy and food industrial processes and for industrial wastewater treatment. Membrane microfiltration has been explored to address this issue because it is simple to operate and low in cost. However, filtration of oil droplets with a size around or less than 1 µm is still a major challenge. Furthermore, the fabrication process for polymeric membranes often uses hazardous organic solvents and petroleum-derived and nonbiodegradable raw materials, which pose additional environmental health and safety risk. In this study, we examined the use of chitosan-based membranes to efficiently remove oil droplets with an average diameter of â¼1 µm. The membranes were fabricated based on the rapid dissolution of chitosan in an alkaline/urea solvent system at a low temperature, thus avoiding the use of any toxic organic solvent. The chitosan membranes were further modified by dopamine and tannic acid (TA). The as-prepared membrane was characterized in terms of surface morphology, pore size distribution, and mechanical strength. The membrane performance was evaluated on a custom-designed crossflow filtration system. The results showed that the modified chitosan membrane with dopamine and TA had a water flux of 230.9 LMH at 1bar transmembrane pressure and oil droplet rejection of 99%. This water flux represented an increase of more than 10 times when compared with the original chitosan membrane without modification. The study also demonstrated excellent antifouling properties of the modified membrane that could achieve near 100% water flux recovery.
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To develop novel norepinephrine transporter (NET)-targeting positron emission tomography (PET) probes with optimal pharmacokinetic properties, a series of meta-bromobenzylguanidine derivatives was synthesized. 4-Fluorodiethoxyethane-3-bromobenzylguanidine (compound 12) showed relatively good affinity for the NET (IC50 = 1.00 ± 0.04 µM). The corresponding radiotracer 18F-12 was prepared in high radiochemical purity (>98%) via a three-step method. The in vitro cellular uptake results demonstrated that 18F-12 was specifically taken up by NET-expressing SK-N-SH cells by the uptake-1 mechanism. Biodistribution studies in mice showed that 18F-12 exhibited high cardiac uptake (10.45 ± 0.66 %ID/g at 5 min p.i. and 6.44 ± 0.40 %ID/g at 120 min p.i.), faster liver clearance, and a lower dose of absorbed radiation than [123I]-labeled meta-iodobenzylguanidine ([123I]MIBG). Small animal PET imaging confirmed the high heart-to-background ratio of 18F-12 and the uptake-1 mechanism specific for the NET in rats, indicating its potential as a promising PET radiotracer for cardiac sympathetic nerve imaging.
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Bromobenzenos/metabolismo , Guanidinas/metabolismo , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/metabolismo , Tomografia por Emissão de Pósitrons , Animais , Bromobenzenos/farmacocinética , Linhagem Celular Tumoral , Radioisótopos de Flúor/farmacocinética , Guanidinas/farmacocinética , Humanos , Camundongos Endogâmicos ICR , Tomografia por Emissão de Pósitrons/métodosRESUMO
The hilly region of western Sichuan is famous for producing Mengding-mountain tea in China. However, it is very easy to enrich fluorine (F) in tea, which recently raised people's concern on fluorosis. In this study, we simulated the local special climate conditions, especially the natural precipitation through column leaching experiment to investigate the effect of fertilization on F desorption from soil. The results suggested different fertilizers could greatly affect desorption of F from soil, but only urea (CO(NH2)2) could significantly and continuously promote the dissolution of F from soil. Furthermore, to reveal the effect of CO(NH2)2 on migration of F from soil to tea, field plots experiment in a tea garden was carried out. The results showed that CO(NH2)2 promoted soil acidification continuously, resulting in the increase of dissolved F and Al content in soil, which were migrated to tea in the form of F-Al complex. Therefore, the key to reducing the F content in tea is to alleviate soil acidification and reduce F-Al complex content in soil. Most importantly, with CO(NH2)2 addition, the contents of F in tea increased significantly from first bud to fifth bud in comparison with those of without CO(NH2)2, especially in 2016, indicating the accelerating and prolonging enrichment of F in tea by adding CO(NH2)2. This study would have important guidance for controlling F mitigation from soil to tea by managing fertilizers application and anthropogenic activities.
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Flúor , Solo , China , Fertilizantes/análise , Humanos , Nitrogênio/análise , Chá , UreiaRESUMO
The positive-charged lipophilic triphenylphosphonium cations (TPPs+ ) have been served as mitochondrial targeting vehicles for the delivery of various probes. In this study, we developed a new method for the preparation of radioiodine-labeled TPPs+ . Four 125 I-labeled TPPs+ , [125 I] 9-[125 I] 12, were prepared from the corresponding triphenylphosphine phenylborate precursors of B 5-B 8 via an optimized copper-catalyzed one-step procedure in high radiochemical yield (>95%). After radio-HPLC purification, the final products could be obtained with high specific activity. Their physicochemical properties, in vitro cellular uptake, and ex vivo mice biodistribution were investigated. The results suggested the 125 I-labeled TPPs+ were lipophilic and could specifically accumulate in the mitochondrial-rich myocardial cells through the mitochondrial membrane potential.