Simultaneous Exposure of Different Nanoparticles Influences Cell Uptake

Drug delivery using nano-sized carriers holds tremendous potential for curing a range of diseases. The internalisation of nanoparticles by cells, however, remains poorly understood, restricting the possibility for optimising entrance into target cells, avoiding off-target cells and evading clearance. The majority of nanoparticle cell uptake studies have been performed in the presence of only the particle of interest; here, we instead report measurements of uptake when the cells are exposed to two different types of nanoparticles at the same time. We used carboxylated polystyrene nanoparticles of two different sizes as a model system and exposed them to HeLa cells in the presence of a biomolecular corona. Using flow cytometry, we quantify the uptake at both average and individual cell level. Consistent with previous literature, we show that uptake of the larger particles is impeded in the presence of competing smaller particles and, conversely, that uptake of the smaller particles is promoted by competing larger particles. While the mechanism(s) underlying these observations remain(s) undetermined, we are partly able to restrain the likely possibilities. In the future, these effects could conceivably be used to enhance uptake of nano-sized particles used for drug delivery, by administering two different types of particles at the same time.

Modelling how cleaner fish approach an ephemeral reward task demonstrates a role for ecologically tuned chunking in the evolution of advanced cognition

What makes cognition “advanced” is an open and not precisely defined question. One perspective involves increasing the complexity of associative learning, from conditioning to learning sequences of events (“chaining”) to representing various cue combinations as “chunks.” Here we develop a weighted graph model to study the mechanism enabling chunking ability and the conditions for its evolution and success, based on the ecology of the cleaner fish Labroides dimidiatus. In some environments, cleaners must learn to serve visitor clients before resident clients, because a visitor leaves if not attended while a resident waits for service. This challenge has been captured in various versions of the ephemeral reward task, which has been proven difficult for a range of cognitively capable species. We show that chaining is the minimal requirement for solving this task in its common simplified laboratory format that involves repeated simultaneous exposure to an ephemeral and permanent food source. Adding ephemeral–ephemeral and permanent–permanent combinations, as cleaners face in the wild, requires individuals to have chunking abilities to solve the task. Importantly, chunking parameters need to be calibrated to ecological conditions in order to produce adaptive decisions. Thus, it is the fine-tuning of this ability, which may be the major target of selection during the evolution of advanced associative learning.

Factors Influencing the Formation of Chemical–Hemoglobin Adducts

Hemoglobin (Hb) adducts have been used as biomarkers for the internal exposure to chemicals. Simultaneous exposure to chemicals that bond with the N-terminal valine of Hb to form adducts, such as glycidol, acrylamide, and glucose, may affect the formation of the individual Hb adducts. In this study, various factors influencing the formation of chemical–Hb adducts were analyzed using in vitro and in vivo systems. In the in vitro assays, the formation of glycidol– and acrylamide–Hb adducts was altered in the presence of glucose, serum albumin, and other chemicals. In contrast, in the in vivo experiments, glycidol– and acrylamide–Hb adduct formation was unchanged in mice exposed to glycidol and acrylamide. The interaction between glycidol and acrylamide with residues other than the N-terminal valine of Hb was analyzed using the protein thermal shift assay. Glycidol and acrylamide also interacted with amino acid residues other than the N-terminal valine of Hb. The presence of other blood components, such as amino acids, may affect the formation of chemical–Hb adducts. Further research is expected to elucidate the remaining unknown factors that affect the formation of chemical–Hb adducts.

Moisture Stability of Perovskite Solar Cells Processed in Supercritical Carbon Dioxide

Performance degradation under environmental conditions currently limits the practical utility of perovskite-based solar cells. The moisture stability of CH3NH3PbI3 perovskite films and solar cells was measured during exposure to three different levels of relative humidity. The films were crystallized at two different temperatures with and without simultaneous exposure to supercritical carbon dioxide. The film crystallinity, optical absorption, and device photoconversion efficiency was measured over time for three relative humidity levels and both crystallization methods. It was determined that film crystallization in supercritical CO2 resulted in significant improvement in moisture stability for films processed at 50 °C, but negligible improvement in stability for films processed at 100 °C.

Antagonistic Effects of Enrofloxacin on Carbendazim-Induced Developmental Toxicity in Zebrafish Embryos

Carbendazim (CAR) and enrofloxacin (ENF) are frequently detected in fruits and meat products, respectively. Since most people consume fruits, vegetables, and meat products, combined exposure is possible, necessitating further evaluation of toxic interactions. In this study, the developmental toxicity of separate and combined exposure was examined in zebrafish embryos. Carbendazim exposure at 0.79 mg/L and above significantly affected developmental parameters, while enrofloxacin alone had no substantial effects on these developmental parameters within the selected concentration range (0.10–0.40 mg/L). Surprisingly, ENF antagonized the CAR-evoked reduction in the 48 hpf (hours post-fertilization) hatching rate and the increases in the 96 hpf malformation and lethality rates. The results revealed that the antagonism might be associated with reciprocal effects of these compounds on metabolism-related genes, such as cyp7a1 and apoa1a. These results reveal a complex interaction between ENF and CAR on metabolic regulation during development and highlight the importance of combined assessment for agents with the potential for simultaneous exposure.

The effectiveness of complex treatment of acute catarrhal mastitis in cows

The article presents data on the study of the therapeutic efficacy of methods for treating cows with acute catarrhal mastitis. The research was carried out on the basis of 2 cattle farms SPK (collective farm) "Kolos" Myasnikovsky district of Rostov region and individual entrepreneur Head of the peasant (farm) farm AA Berekchiyan Myasnikovsky district of the Rostov region, as well as on the basis of the North Caucasian zonal research veterinary institute - a branch of the Federal State Budgetary Institution "Federal Rostov Agrarian Scientific Center". To study the therapeutic efficacy of the treatment regimen for acute catarrhal mastitis, 2 groups of animals (experimental and control) were also formed according to the principle of analogous pairs, 15 animals each. Control cows were injected with the antibacterial drug amoxicillin LA 15% twice with an interval of 48 hours at the rate of 1 ml of the drug per 10 kg of animal body weight. The drug was administered fractionally, divided into 2 injections. The animals of the experimental group were also injected with the semisynthetic antibiotic amoxicillin LA 15% twice with an interval of 48 hours at the rate of 1 ml of the drug per 10 kg of the animal's body weight. The treatment regimen was supplemented by exposing the animal's body to pulsed low-intensity infrared laser radiation with simultaneous exposure to pulsed incoherent infrared and red radiation and a constant magnetic field in the infiltrate area once a day at the rate of 5 minutes per 10 cm2 of the affected area for 5-7 days. In the course of our research, it was found that therapy for catarrhal mastitis using pulsed low-intensity infrared laser radiation with simultaneous exposure to pulsed incoherent infrared and red radiation and a constant magnetic field in the infiltrate area once a day, as well as the semisynthetic antibiotic amoxicillin LA 15% twice with at intervals of 48 hours showed a high degree of effectiveness. This is confirmed by the rapid recovery of the clinical picture, physiological parameters, and morphological data of the blood of experimental animals. The therapeutic efficiency of the proposed method of treatment was 100%, recovery occurred on average in 3.9 ± 0.15 days. The signs of the inflammatory process disappeared gradually, however, by the 3rd day of treatment, the secretion of milk was completely restored and a significant improvement in the condition of the animals was noted.

Effects of Simultaneous Exposure to a Western Diet and Wheel-Running Training on Brain Energy Metabolism in Female Rats

Background: In the pathogenesis of central nervous system disorders (e.g., neurodegenerative), an important role is attributed to an unhealthy lifestyle affecting brain energy metabolism. Physical activity in the prevention and treatment of lifestyle-related diseases is getting increasing attention. Methods: We performed a series of assessments in adult female Long Evans rats subjected to 6 weeks of Western diet feeding and wheel-running training. A control group of lean rats was fed with a standard diet. In all experimental groups, we measured physiological parameters (animal weights, body composition, serum metabolic parameters). We assessed the impact of simultaneous exposure to a Western diet and wheel running on the cerebrocortical protein expression (global proteomic profiling), and in the second part of the experiment, we measured the cortical levels of protein related to brain metabolism (Western blot). Results: Western diet led to an obese phenotype and induced changes in the serum metabolic parameters. Wheel running did not reduce animal weights or fat mass but significantly decreased serum glucose level. The global proteome analysis revealed that the altered proteins were functionally annotated as they were involved mostly in metabolic pathways. Western blot analysis showed the downregulation of the mitochondrial protein—Acyl-CoA dehydrogenase family member 9, hexokinase 1 (HK1)—enzyme involved in principal glucose metabolism pathways and monocarboxylate transporter 2 (MCT2). Wheel running reversed this decline in the cortical levels of HK1 and MCT2. Conclusion: The cerebrocortical proteome is affected by a combination of physical activity and Western diet in female rats. An analysis of the cortical proteins involved in brain energy metabolism provides a valuable basis for the deeper investigation of changes in the brain structure and function induced by simultaneous exposure to a Western diet and physical activity.

Comprehensive Assessment of Local Population Chemical Exposome by Combination of Organic Pollutant- and Metal-Multi-Residue Analysis in Hair

Awareness of the adverse effects of exposure to pollutant mixtures, possibly much more severe than individual chemicals, has drawn attention towards the necessity of using multi-residue methods to obtain the most possible comprehensive information on exposome. Among the different biological matrices used for exposure assessment, hair enables to detect the largest number of chemicals, including many classes such as persistent pollutants, hydrophilic metabolites and metals. Most biomonitoring studies are however focused on a limited number of pollutants and only give a partial information on exposure. Combining several multi-residue methods, the present study aimed at assessing the exposure of a population to an extensive variety of chemicals by hair analysis. One hair sample was collected from each participant (55 children and 134 adults). Samples were analysed with three different multi-residue methods, targeting, respectively, 152 organic pollutants (pesticides, PCBs, bisphenols, PBDEs), 62 polycyclic aromatic hydrocarbons (PAHs) and metabolites, nicotine and cotinine and 36 metals. From 33 to 70 organic chemicals were detected in each child’s hair sample, and from 34 up to 74 in adults. From 7 to 26 PAH were detected per child, and 7 to 21 in adults. Twenty-three to 27 metals were detected per child and 21 to 28 per adult. The highest median concentration were observed for zinc (143 μg /mg in children; 164 μg /mg in adults), bisphenol A (95.9 pg/mg in children; 64.7 pg/mg in adults) and nicotine (66.4 pg/mg in children; 51.9 pg/mg in adults). The present study provides the most comprehensive exposure assessment ever and highlights the simultaneous exposure to multiple classes of pollutants in the general population. The results support the use of multi-residue methods for future studies on exposure-associated effects, to document exposome and better consider the effect of chemical mixtures.

Co-Exposure to Toluene and Noise Made Synergistic and Antagonistic Effects on Some Neurotoxic Parameters in New Zealand White Rabbits

Introduction: Numerous physical and chemical agents can induce destructive effects on the brain tissue. Noise and toluene, which are some of these harmful agents, have significant adverse effects on the brain tissue. This work aims to investigate the neurotoxic changes induced by co-exposure to toluene and noise. Methods: Totally, 24 male white New Zealand rabbits were randomly segregated into 4 groups including toluene exposure, noise exposure, co-exposure to noise and toluene, and control. This in-vivo study tested the neurotoxic effects of exposure to 1000 ppm toluene and 100 dB noise during two weeks (8 h/day). The serum levels of brain-derived neurotrophic factor-α (BDNF-α) and malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase levels in the brain tissue were measured. Moreover, hematoxylin and eosin staining was utilized for brain pathological analysis. Results: Exposure to noise increased TAC level in the cerebral cortex. Co- exposure to toluene and noise increased the serum level of BDNF-α. Nevertheless, exposure to noise decreased the level of BDNF-α in serum. On the other hand, hispathological examinations using hematoxylin-eosin (H&E) exhibited that different signs of inflammation such as lymphocyte infiltration, pyknosis, vacuolization, and chromatolysis were induced by exposure to noise and toluene in the cerebellum, hippocampus, and frontal section in the brain tissue. In addition, simultaneous exposure to toluene and noise induced antagonistic and synergistic changes on some neurotoxic parameters. Conclusion: Exposure to noise and toluene, which caused inflammation in the brain tissue cells, could be a noticeable risk factor for neurological system.

Pathophysiological bases of maladjustment formation in high mountains and polar zones

The pathophysiological features of the development of maladjustment under mountain-cold conditions as a manifestation of the syndrome of mutual burdening are considered. In this study, contents of various literary sources, characterizing a persons resistance to the effects of a complex of factors under high mountains and polar zones conditions, were analyzed. With the simultaneous exposure to hypoxia and hypothermia from a pathophysiological point of view, intersecting links of terminological paths, often having diametrically opposite dynamics of changes in the characterized concepts, will be significant. Thus, in the terminological mitochondrial pathway of energy metabolism, uncoupling proteins are present, which, to increase the resistance to hypothermia, should be activated to switch the energy metabolism to predominantly use fatty acids. However, hypoxic conditions should be suppressed to maintain the level of adenosine triphosphate acid available for cells. In the terminological tract of compensatory reactions in response to hypoxemia, the volume of pulmonary ventilation is released, which must increase to improve tolerance to hypoxia, which, under mountain-cold conditions, increased heat loss and promote the deterioration of the condition, i.e., tolerance to low temperatures. Under hypoxic and hypothermic conditions, a synergistic interaction can form, which can be manifested by the development of a syndrome of mutual burdening, which will result in a significant decrease in the functional capabilities of the body, result, and productivity. Maladjustment to mountain cold, with maximum probability, will manifest as disorders of the central nervous system, decreased physical performance, depletion of the functional and regulatory reserves of the body, functional immunodeficiency, decreased regenerative potential, and development of endogenous intoxication. With a high degree of probability, a significant synergistic interaction of hypoxia and hypothermia can be found in relation to the indicators of pulmonary ventilation, blood gases (hypercapnia), acidbase balance (gas alkalosis and lactic acidosis), heart rate (tachycardia), blood pressure (hypotension), central venous pressure (increase), blood viscosity (increase) and its coagulability (hypercoagulation), peroxide and free radical oxidation (activation), and protein catabolism (increase). These changes will negatively affect the functional state of specialists performing complex professional tasks in polar latitudes.