Herrerabeck4584

Nanoparticles with encapsulated sulindac in the core and doxorubicin (DOX) in the shell demonstrated target specificity and enhanced internalization with synergistic cytotoxic effects with a 30-fold reduction in IC50 in DOX-resistant, triple-negative MDA-MB 231 breast cancer cells. Nanoparticles were radiolabeled with 131I radioisotopes with ≥80% efficiency while retaining its gal-3 binding property. Biodistribution studies of radiolabeled placebo nanoparticles and drug-loaded CPDA nanoparticles demonstrated proof of concept of gal-3 targeting seen as preferential accumulation in the gal-3-expressing tissues of the gastric tract. The CPDA core-shell nanoparticles are thus promising platforms for gal-3 targeting and inhibition of gal-3-mediated processes involved in cancer progression with a potential of radiolabeling for in vivo monitoring or delivering therapeutic doses of radiation and on-demand triggered, target-specific drug release.Rapalogues are a unique class of drugs with both cytostatic and immunosuppressive properties. Two founding members, Rapamycin (Rapa) and its chemical derivative Everolimus (Eve) are extremely potent, but their clinical use presents multiple challenges. Being water insoluble, administration is restricted to the oral route, which results in a low bioavailability of less then 10%. Human studies of rapalogues are reported to yield a high blood to plasma ratio and poor correlation between blood concentration and dose. Moreover, treatment results in dose-limiting toxicities like stomatitis and pneumonitis, which often leads to discontinuation of therapy. We previously reported an elastin-like polypeptide (ELP) decorated with two-headed FKBP rapalogue-binding domains. Called 'FAF,' this biomacromolecular drug-carrier solubilizes, retargets, and releases rapalogues within disease sites. FAF-rapalogue formulations are free of co-solvents or surfactants, which promotes their parenteral administration. When given subcutaneously (SC) in a mouse model of hormone receptor positive (HR+) breast cancer, FAF-Rapa significantly suppressed tumor growth compared to an oral formulation of Eve (Affinitor®). Additionally, mTOR, the pharmacological target of rapalogues was inhibited to a greater extent in tumors of FAF-Rapa and FAF-Eve groups compared to mice that received oral Eve. No signaling suppression was detected in the liver and spleen, which were evaluated to represent off-target organs exposed to the circulating formulation.Identifying potential persistent organic pollutants (POPs) and persistent, bioaccumulative, and toxic (PBT) substances from industrial chemical inventories are essential for chemical risk assessment, management, and pollution control. Inspired by the connections between chemical structures and their properties, a deep convolutional neural network (DCNN) model was developed to screen potential PBT/POP-like chemicals. Phenylbutyrate For each chemical, a two-dimensional molecular descriptor representation matrix based on 2424 molecular descriptors was used as the model input. The DCNN model was trained via a supervised learning algorithm with 1306 PBT/POP-like chemicals and 9990 chemicals currently known as non-POPs/PBTs. The model can achieve an average prediction accuracy of 95.3 ± 0.6% and an F-measurement of 79.3 ± 2.5% for PBT/POP-like chemicals (positive samples only) on external data sets. The DCNN model was further evaluated with 52 experimentally determined PBT chemicals in the REACH PBT assessment list and correctly recognized 47 chemicals as PBT/non-PBT chemicals. The DCNN model yielded a total of 4011 suspected PBT/POP like chemicals from 58 079 chemicals merged from five published industrial chemical lists. The proportions of PBT/POP-like substances in the chemical inventories were 6.9-7.8%, higher than a previous estimate of 3-5%. Although additional PBT/POP chemicals were identified, no new family of PBT/POP-like chemicals was observed.The magnetic properties of the spin-5/2 double molybdate LiFe(MoO4)2 have been characterized by heat capacity, magnetic susceptibility, and neutron powder diffraction techniques. Unlike the multiferroic system LiFe(WO4)2 which exhibits two successive magnetic transitions, LiFe(MoO4)2 undergoes only one antiferromagnetic transition at TN ∼ 23.8 K. Its antiferromagnetic magnetic structure with the commensurate propagation vector k = (0, 0.5, 0) has been determined. Density functional theory calculations confirm the antiferromagnetic ground state and provide a numerical estimate of the relevant exchange coupling constants.A widely used microbial source tracking (MST) technique, quantitative polymerase chain reaction (qPCR), quantifies host-specific gene abundance in polluted water to identify and prioritize contamination sources. This study characterized the effects of a qPCR data analysis using the sample PCR efficiencies (the LinRegPCR model) on gene abundance and compared it with the standard curve-based method (the mixed model). Five qPCR assays were evaluated the universal GenBac3, human-specific HF183/BFDrev and CPQ_056, swine-specific Pig-2-Bac, and cattle-specific Bac3qPCR assays. The LinRegPCR model increased low-copy amplification, especially in the HF183/BFDrev assay, thus lowering the specificity to less than the recommended value of 0.80. Up to 1.41 log10 copies/g and 0.41 log10 copies/100 mL differences were observed for composite fecal and sewage samples (n=147) by the LinRegPCR approach, corresponding to an 18.2% increase and 6.4% decrease, respectively. Freshwater samples (n=48) demonstrated a maximum of 1.95 log10 copies/100 mL difference between the two models. Identical attributing sources by both models were shown in 54.55% of environmental samples; meanwhile, the LinRegPCR approach improved the inability to identify sources by the mixed model in 29.55% of the samples. This study emphasizes the need for a standardized data analysis protocol for qPCR MST assays for interlaboratory consistency and comparability.A bifunctional molecule containing both a bidentate binding site for metal ions and an aminopyrimidine H-bond donor-acceptor site has been synthesized, and its properties, in its free and coordinated forms, have been established in solution and in the solid state by analytical and spectroscopic methods as well as by X-ray structure determinations. Structural characterization has shown that it forms a one-dimensional H-bonded polymeric assembly in the solid state, while spectroscopic measurements indicate that it also aggregates in solution. The reaction of a simple Fe(II) salt with this assembly results in the emergence of two geometrical isomers of the complex [FeL3](BF4)2·9H2O-C1 (meridional, mer) and [FeL3]2(SiF6)(BF4)2·12H2O-C2 (facial, fac). While, complex C1 in the solid state generates a one-dimensional H-bonded polymer involving just two ligands on each Fe center, with the chirality of the complex units alternating along the polymer chain, the structure of complex C2 shows NH···N interactions seen in both the ligand and mer complex (C1) structures to be completely absent.