Mass spectrometry-based DNA adductomics is an emerging approach for the human biomonitoring of hazardous chemicals. A mass spectral database of DNA adducts will be created for the scientific community to investigate the associations between chemical exposures, DNA damage, and disease risk.Untreated sewer overflows can contaminate receiving waters with micropollutants. Although concentrations of discharged micropollutants can be ecotoxicologically relevant, only limited data is available to assess occurrence and spatial differences among sewer overflow catchments. Therefore, we present an innovative type of data obtained with passive samplers at 20 combined sewer overflow sites (2-7 events per site; 95 events in total). The data sheds light on concentration ranges for 13 representative polar organic micropollutants and shows that micropollutants in both municipal wastewater and stormwater can be relevant sources of contaminants. We identify indicator micropollutants for further studies benzotriazole (80% interquantile of time-weighted average concentration 250-4,800 ng/L), carbamazepine (33-910 ng/L), diclofenac (78-1,000 ng/L), carbendazim (21-900 ng/L), diazinon (2.1-53 ng/L), diuron (22-1,100 ng/L), mecoprop (198-5,300 ng/L), metolachlor (6-230 ng/L), and terbutryn (29-810 ng/L). These concentration estimates are assumed to be on the safe side for comparison with environmental quality standards (EQS). A majority of sewer overflow sites (13 of 20) show discharge concentrations above acute EQS for at least one micropollutant and thus would have to rely on dilution by receiving waters to not exceed any EQS. The intersite variability among sewer overflows exceed the within-site variability. Hence, future monitoring studies should cover more sewer overflow sites. No correlation could be found with event durations, specific storage volume or land use data, thus showing the complexity of micropollutant occurrence and indicating that other factors led to the observed high spatial variability. In conclusion, our results clearly show the potential relevance of micropollutants in sewer overflows and the need to assess site-specific measures.Rapid liver and spleen opsonization of systemically administered nanoparticles (NPs) for in vivo applications remains the Achilles' heel of nanomedicine, allowing only a small fraction of the materials to reach the intended target tissue. https://www.selleckchem.com/products/cc-930.html Although focusing on diseases that reside in the natural disposal organs for nanoparticles is a viable option, it limits the plurality of lesions that could benefit from nanomedical interventions. Here we designed a theranostic nanoplatform consisting of reactive oxygen (ROS)-generating titanium dioxide (TiO2) NPs, coated with a tumor-targeting agent, transferrin (Tf), and radiolabeled with a radionuclide (89Zr) for targeting bone marrow, imaging the distribution of the NPs, and stimulating ROS generation for cell killing. Radiolabeling of TiO2 NPs with 89Zr afforded thermodynamically and kinetically stable chelate-free 89Zr-TiO2-Tf NPs without altering the NP morphology. Treatment of multiple myeloma (MM) cells, a disease of plasma cells originating in the bone marrow, with 89Zr-TiO2-Tf generated cytotoxic ROS to induce cancer cell killing via the apoptosis pathway. Positron emission tomography/X-ray computed tomography (PET/CT) imaging and tissue biodistribution studies revealed that in vivo administration of 89Zr-TiO2-Tf in **** leveraged the osteotropic effect of 89Zr to selectively localize about 70% of the injected radioactivity in mouse bone tissue. A combination of small-animal PET/CT imaging of NP distribution and bioluminescence imaging of cancer progression showed that a single-dose 89Zr-TiO2-Tf treatment in a disseminated MM mouse model completely inhibited cancer growth at euthanasia of untreated **** and at least doubled the survival of treated ****. Treatment of the **** with cold Zr-TiO2-Tf, 89Zr-oxalate, or 89Zr-Tf had no therapeutic benefit compared to untreated controls. This study reveals an effective radionuclide sensitizing nanophototherapy paradigm for the treatment of MM and possibly other bone-associated malignancies.This paper investigates a strategy to convert hydrophilic cellulose nanofibrils (CNF) into a hydrophobic highly cross-linked network made of cellulose nanofibrils and inorganic nanoparticles. First, the cellulose nanofibrils were chemically modified through an esterification reaction to produce a nanocellulose-based macroinitiator. Barium titanate (BaTiO3, BTO) nanoparticles were surface-modified by introducing a specific monomer on their outer-shell surface. Finally, we studied the ability of the nanocellulose-based macroinitiator to initiate a single electron transfer living radical polymerization of stearyl acrylate (SA) in the presence of the surface-modified nanoparticles. The BTO nanoparticles will transfer new properties to the nanocellulose network and act as a cross-linking agent between the nanocellulose fibrils, while the monomer (SA) directly influences the hydrophilic-lipophilic balance. The pristine CNF and the nanoparticle cross-linked CNF are characterized by FTIR, SEM, and solid-state 13C NMR. Rheological and dynamic mechanical analyses revealed a high dregee of cross-linking.The production of large quantities of artificial spider silk fibers that match the mechanical properties of the native material has turned out to be challenging. Recent advancements in the field make biomimetic spinning approaches an attractive way forward since they allow the spider silk proteins to assemble into the secondary, tertiary, and quaternary structures that are characteristic of the native silk fiber. Straining flow spinning (SFS) is a newly developed and versatile method that allows production under a wide range of processing conditions. Here, we use a recombinant spider silk protein that shows unprecedented water solubility and that is capable of native-like assembly, and we spin it into fibers by the SFS technique. We show that fibers may be spun using different hydrodynamical and chemical conditions and conclude that these spinning conditions affect fiber mechanics. In particular, it was found that the addition of acetonitrile and polyethylene glycol to the collection bath results in fibers with increased β-sheet content and improved mechanical properties.
Mass spectrometry-based DNA adductomics is an emerging approach for the human biomonitoring of hazardous chemicals. A mass spectral database of DNA adducts will be created for the scientific community to investigate the associations between chemical exposures, DNA damage, and disease risk.Untreated sewer overflows can contaminate receiving waters with micropollutants. Although concentrations of discharged micropollutants can be ecotoxicologically relevant, only limited data is available to assess occurrence and spatial differences among sewer overflow catchments. Therefore, we present an innovative type of data obtained with passive samplers at 20 combined sewer overflow sites (2-7 events per site; 95 events in total). The data sheds light on concentration ranges for 13 representative polar organic micropollutants and shows that micropollutants in both municipal wastewater and stormwater can be relevant sources of contaminants. We identify indicator micropollutants for further studies benzotriazole (80% interquantile of time-weighted average concentration 250-4,800 ng/L), carbamazepine (33-910 ng/L), diclofenac (78-1,000 ng/L), carbendazim (21-900 ng/L), diazinon (2.1-53 ng/L), diuron (22-1,100 ng/L), mecoprop (198-5,300 ng/L), metolachlor (6-230 ng/L), and terbutryn (29-810 ng/L). These concentration estimates are assumed to be on the safe side for comparison with environmental quality standards (EQS). A majority of sewer overflow sites (13 of 20) show discharge concentrations above acute EQS for at least one micropollutant and thus would have to rely on dilution by receiving waters to not exceed any EQS. The intersite variability among sewer overflows exceed the within-site variability. Hence, future monitoring studies should cover more sewer overflow sites. No correlation could be found with event durations, specific storage volume or land use data, thus showing the complexity of micropollutant occurrence and indicating that other factors led to the observed high spatial variability. In conclusion, our results clearly show the potential relevance of micropollutants in sewer overflows and the need to assess site-specific measures.Rapid liver and spleen opsonization of systemically administered nanoparticles (NPs) for in vivo applications remains the Achilles' heel of nanomedicine, allowing only a small fraction of the materials to reach the intended target tissue. https://www.selleckchem.com/products/cc-930.html Although focusing on diseases that reside in the natural disposal organs for nanoparticles is a viable option, it limits the plurality of lesions that could benefit from nanomedical interventions. Here we designed a theranostic nanoplatform consisting of reactive oxygen (ROS)-generating titanium dioxide (TiO2) NPs, coated with a tumor-targeting agent, transferrin (Tf), and radiolabeled with a radionuclide (89Zr) for targeting bone marrow, imaging the distribution of the NPs, and stimulating ROS generation for cell killing. Radiolabeling of TiO2 NPs with 89Zr afforded thermodynamically and kinetically stable chelate-free 89Zr-TiO2-Tf NPs without altering the NP morphology. Treatment of multiple myeloma (MM) cells, a disease of plasma cells originating in the bone marrow, with 89Zr-TiO2-Tf generated cytotoxic ROS to induce cancer cell killing via the apoptosis pathway. Positron emission tomography/X-ray computed tomography (PET/CT) imaging and tissue biodistribution studies revealed that in vivo administration of 89Zr-TiO2-Tf in mice leveraged the osteotropic effect of 89Zr to selectively localize about 70% of the injected radioactivity in mouse bone tissue. A combination of small-animal PET/CT imaging of NP distribution and bioluminescence imaging of cancer progression showed that a single-dose 89Zr-TiO2-Tf treatment in a disseminated MM mouse model completely inhibited cancer growth at euthanasia of untreated mice and at least doubled the survival of treated mice. Treatment of the mice with cold Zr-TiO2-Tf, 89Zr-oxalate, or 89Zr-Tf had no therapeutic benefit compared to untreated controls. This study reveals an effective radionuclide sensitizing nanophototherapy paradigm for the treatment of MM and possibly other bone-associated malignancies.This paper investigates a strategy to convert hydrophilic cellulose nanofibrils (CNF) into a hydrophobic highly cross-linked network made of cellulose nanofibrils and inorganic nanoparticles. First, the cellulose nanofibrils were chemically modified through an esterification reaction to produce a nanocellulose-based macroinitiator. Barium titanate (BaTiO3, BTO) nanoparticles were surface-modified by introducing a specific monomer on their outer-shell surface. Finally, we studied the ability of the nanocellulose-based macroinitiator to initiate a single electron transfer living radical polymerization of stearyl acrylate (SA) in the presence of the surface-modified nanoparticles. The BTO nanoparticles will transfer new properties to the nanocellulose network and act as a cross-linking agent between the nanocellulose fibrils, while the monomer (SA) directly influences the hydrophilic-lipophilic balance. The pristine CNF and the nanoparticle cross-linked CNF are characterized by FTIR, SEM, and solid-state 13C NMR. Rheological and dynamic mechanical analyses revealed a high dregee of cross-linking.The production of large quantities of artificial spider silk fibers that match the mechanical properties of the native material has turned out to be challenging. Recent advancements in the field make biomimetic spinning approaches an attractive way forward since they allow the spider silk proteins to assemble into the secondary, tertiary, and quaternary structures that are characteristic of the native silk fiber. Straining flow spinning (SFS) is a newly developed and versatile method that allows production under a wide range of processing conditions. Here, we use a recombinant spider silk protein that shows unprecedented water solubility and that is capable of native-like assembly, and we spin it into fibers by the SFS technique. We show that fibers may be spun using different hydrodynamical and chemical conditions and conclude that these spinning conditions affect fiber mechanics. In particular, it was found that the addition of acetonitrile and polyethylene glycol to the collection bath results in fibers with increased β-sheet content and improved mechanical properties.
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