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Invasive alien plants (IAPs) present a severe threat to native ecosystems and biodiversity. Comprehending the potential distribution patterns of these plant invaders and their responses to climate change is essential. Parthenium hysterophorus, native to the Americas, has become an aggressively invasive species since its introduction to China in the 1930s. This study aims to collect and reconstruct the historical occurrence and invasion of P. hysterophorus. Using the optimal MaxEnt model, the potential geographical distributions of P. hysterophorus were predicted based on screened species occurrences and environmental variables under the current and three future scenarios in the 2030s, 2050s, and 2070s (i.e., SSP1-2.6, SSP2-4.5, and SSP5-8.5), and the invasion risk of P. hysterophorus in Chinese cities, croplands, forests, and grasslands was assessed. The results show that: (1) The species initially invaded highly suitable areas and further spread to regions with non-analogous climate conditions. (2) Under the current climatic conditions, the overall potential distribution of P. hysterophorus is characterized by more in the southeast and less in the northwest. Climate variables, including mean annual temperature (bio1), precipitation in the wettest month (bio13), isothermality (bio3), and temperature seasonality (bio4), are the primary factors influencing its distribution. (3) The potential distribution of P. hysterophorus will expand further under future climate scenarios, particularly toward higher latitudes. (4) Forests and crop lands are the areas with the most serious potential invasion risk of P. hysterophorus. Therefore, we suggest that the government should strengthen the monitoring and management of P. hysterophorus to prevent its spread and protect agro-ecosystems and human habitats. Depending on the potential risk areas, measures such as quarantine, removal, and publicity should be taken to mitigate the threat of P. hysterophorus invasion and to raise awareness of P. hysterophorus invasion prevention.
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Macrosaccus morrisella (Fitch) (Lepidoptera: Gracillariidae) is a leaf-mining microlepidopteran native to North America recently reported feeding on soybean in the United States and Canada. Control methods for the management of this pest remain unknown. The insecticides Agri-Mek SC (abamectin) and Endigo ZXC (lambda-cyhalothrin + thiamethoxam) were evaluated for: (i) effects against immature stages of M. morrisella in potted soybean plants; (ii) effects against adults of M. morrisella through different routes of exposure; and (iii) efficacy of field applications against M. morrisella. In the experiment with immature stages, when either insecticide was applied to potted plants with M. morrisella in serpentine or blotch mines, significantly fewer adults emerged compared to the untreated plants. In contrast, adult emergence from potted plants treated with either insecticide when M. morrisella was in tentiform mines did not differ from untreated plants. In the experiment with adults, the survival of M. morrisella exposed to either insecticide through oral exposure or residual contact + oral exposure was significantly lower than that for residual contact exposure alone, which in turn was lower than the untreated control. Within each exposure route, the response to the 2 insecticides did not differ. In the field experiment, at 21 days after insecticide application, the mean percentage of leaf area mined was significantly lower in plots treated with Endigo ZCX compared to plots treated with Agri-Mek SC or those left untreated. These results suggest that Endigo ZXC and to a lesser extent Agri-Mek SC may have potential for management of M. morrisella.
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In a quest to find eco-friendly materials from renewable resources, researchers have focused on cellulose materials, which is the primary reinforcing component of plant cell walls. Nanocellulose is at the forefront of research due to its wide range of sources, biocompatibility, large surface area and tunable surface chemistry. It has gained considerable attention in various industries as a nano-reinforcement for polymer matrices due to its hierarchical structure (medical and healthcare, oil and gas, packaging, paper, board, composites, printed and flexible electronics, 3D printing, aerogels). In this paper, we have reviewed the recent advances in nanocellulose production, physical properties, structural characterization, surface modification strategies, pretreatment methods, applications, limitations and future directions. This review emphasizes the quantification of nanocellulose extraction and applications of the most prevalent areas of nanocellulose research. In view of its increasing and broader applications, the demand for nanocellulose is expected to increase in the future.
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BACKGROUND: Children's active travel to school is associated with physical activity and thus health. Safe Routes to School (SR2S) programs identify 'safe routes' to promote children's active travel to school. No field audit tool exists specifically to assess the microscale built environment of these 'safe routes' within Australia. This study describes the reliability assessment of the Field Audit for Children's Active Transport to School (FACTS) tool. METHODS: The FACTS tool was developed using a multi-step process, including a literature search, expert opinion, and pilot testing. For the reliability assessment, two trained auditors collected data at eight schools over three weeks in April 2021. For inter-rater reliability, auditors conducted audits on the 'safe routes' for the same six schools. For intra-rater reliability, auditors conducted repeat measures on the 'safe routes' for four schools each (eight schools total), including three different schools each from the six used for inter-rater reliability and one additional school. Item-by-item reliability was assessed using Cohen's Kappa, Cohen's Weighted Kappa, and percentage agreement. The reliability of calculated domain scores was assessed using intraclass correlation coefficients. RESULTS: For inter-rater reliability, 31 of the 45 (68.9%) items had moderate to almost perfect agreement, seven items (15.6%) had below moderate agreement, and a Kappa statistic could not be calculated for seven items (15.6%) due to constant values. For intra-rater reliability, 37 of the 45 (82.2%) items had moderate to almost perfect agreement, two items (4.4%) had below moderate agreement, and a Kappa statistic could not be calculated for six items (13.3%) due to constant values. For inter- and intra-rater reliability of the segment domain scores, three of the four domains had substantial to almost perfect agreement. For inter- and intra-rater reliability of the crossing domain scores, all four domains had moderate to almost perfect agreement. For inter- and intra-rater reliability of the segment, crossing, route, and school scores, all had substantial to perfect agreement. CONCLUSIONS: The FACTS tool can reliably characterise the microscale built environment of promoted 'safe routes' for their use within SR2S programs, and should be considered for use in future SR2S programs within the suburban Australian context.
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Instituições Acadêmicas , Meios de Transporte , Humanos , Criança , Reprodutibilidade dos Testes , Austrália , Exercício FísicoRESUMO
BACKGROUND: Cannabis legalization has made cannabis accessible via dispensaries which sell a wide variety of cannabis products. Importantly, the various routes of administration are associated with differing consequences. As such, it's crucial to understand the prevalence and correlates of different cannabis products. Unfortunately, research has yet to examine the prevalence of certain forms of cannabis use, and little is known about the prevalence of using multiple forms of cannabis, and whether individual-level factors are associated with using different forms of cannabis. METHODS: The current study uses data from the 2022 National Survey on Drug Use and Health (NSDUH) to examine the prevalence and correlates of eight different types of cannabis use (smoking, vaping, eating/drinking, dabbing, drops/lozenges, topical, pills, and other), as well as a cannabis variety scale, on samples of adult and adolescent cannabis users. RESULTS: The results suggest that certain routes of administration are more prevalent than others and that these patterns are fairly consistent between adults and adolescents. Similarly, for both adults and adolescents, the majority of users used more than one cannabis product. Lastly, several individual-level factors are associated with the various forms of cannabis use and many of these associations vary by the route of administration examined. CONCLUSIONS: The results of the current study demonstrate that there are differences among cannabis users. If we can develop an understanding of who uses the various forms of cannabis, we could identify the users of the more dangerous forms and provide these individuals with more resources.
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Uso da Maconha , Humanos , Adolescente , Estados Unidos/epidemiologia , Masculino , Feminino , Prevalência , Adulto , Adulto Jovem , Uso da Maconha/epidemiologia , Fumar Maconha/epidemiologia , Vias de Administração de Medicamentos , Pessoa de Meia-Idade , Vaping/epidemiologiaRESUMO
BACKGROUND: Nocardia, a rare but potentially fatal pathogen, can induce systemic infections with diverse manifestations. This study aimed to investigate the tissue and organ damage caused by Nocardia farcinica (N. farcinica) in mice via different infection routes, evaluate the resulting host immune responses, and assess its invasiveness in brain tissue. METHODS: BALB/c mice were infected with N. farcinica through intranasal, intraperitoneal, and intravenous routes (doses: 1 × 10^8, 1 × 10^7, 1 × 10^7 CFU in 50 µl PBS). Over a 7-day period, body temperature, weight, and mortality were monitored, and samples were collected for histopathological analysis and bacterial load assessment. Serum was isolated for cytokine detection via ELISA. For RNA-seq analysis, mice were infected with 1 × 107 CFU through three infection routes, after which brain tissue was harvested. RESULTS: Intraperitoneal and intravenous N. farcinica infections caused significant clinical symptoms, mortality, and neural disruption in mice, resulting in severe systemic infection. Conversely, intranasal infection primarily affected the lungs without causing significant damage to other organs. Intraperitoneal and intravenous infections significantly increased serum cytokines, particularly TNF-α and IFN-γ. RNA-seq analysis of brains from intravenously infected mice revealed significant differential gene expression, whereas the intranasal and intraperitoneal routes showed limited differences (only three genes). The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in the intravenous group were primarily related to immune processes. CONCLUSION: The study demonstrated that intravenous N. farcinica infection induces significant clinical symptoms, triggers an inflammatory response, damages multiple organs, and leads to systemic infections.
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Encéfalo , Citocinas , Camundongos Endogâmicos BALB C , Nocardiose , Nocardia , Animais , Nocardia/genética , Nocardiose/microbiologia , Nocardiose/imunologia , Camundongos , Citocinas/sangue , Feminino , Encéfalo/microbiologia , Encéfalo/patologia , Pulmão/microbiologia , Pulmão/patologia , Modelos Animais de Doenças , Carga BacterianaRESUMO
China's rapid expansion of civil aviation has led to an increase in pollution-related issues, causing adverse health effects on populations near airports and downwind. Accurately quantifying aviation emissions is essential for effective emission management. Here, we developed a high-resolution aviation emissions inventory for China by employing a bottom-up approach that relied on daily flight schedules. By using the Aeronautical Information Publication (AIP) to reproduce real-world flight routes rather than conventional great-circle routes, we improved the accuracy of emissions and investigated the potential for reducing these emissions. Our findings demonstrated substantial variations in domestic civil aviation emissions both spatially and temporally. Emissions peaked in most provinces during Chinese holidays, particularly the Chinese Lunar New Year and summer holidays, highlighting the importance of detailed activity data for accurate emissions calculations. Therefore, we recommend extensive utilization of real-world flight routes, particularly in areas with limited Automatic Dependent Surveillance-Broadcast (ADS-B) coverage since they provide more accurate representations of actual flight trajectories. Our study also identified regions like Shaanxi, Sichuan, Beijing, and their surroundings having considerable potential for emission reduction due to substantial deviations from great-circle routes. This approach can enhance the accuracy and spatiotemporal resolution of aviation emissions at national and global scales throughout the year, without relying on extensive, long-term real-time flight trajectories. Additionally, it provides a unique way to quantify the potential for emission reductions across provinces in civil aviation, ultimately contributing to mitigating pollution-related health impacts from aviation emissions and promoting a more sustainable aviation industry.
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RSV infection remains a serious threat to the children all over the world, especially, in the low-middle income countries. Vaccine delivery via the mucosa holds great potential for inducing local immune responses in the respiratory tract. Previously, we reported the development of highly immunogenic RSV virus-like-particles (RSV-VLPs) based on the conformationally stable prefusogenic-F protein (preFg), glycoprotein and matrix protein. Here, to explore whether mucosal delivery of RSV-VLPs is an effective strategy to induce RSV-specific mucosal and systemic immunity, RSV-VLPs were administered via the nasal, sublingual and pulmonary routes to BALB/c mice. The results demonstrate that immunization with the VLPs via the mucosal routes induced minimal mucosal response and yet facilitated modest levels of serum IgG antibodies, enhanced T cell responses and the expression of the lung-homing marker CXCR3 on splenocytes. Immunization with VLPs via all three mucosal routes provided protection against RSV challenge with no signs of RSV induced pathology.
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Anticorpos Antivirais , Camundongos Endogâmicos BALB C , Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vacinas de Partículas Semelhantes a Vírus , Proteínas Virais de Fusão , Proteínas da Matriz Viral , Animais , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/imunologia , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Camundongos , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Proteínas Virais de Fusão/imunologia , Proteínas Virais de Fusão/genética , Proteínas Virais de Fusão/administração & dosagem , Feminino , Proteínas da Matriz Viral/imunologia , Proteínas da Matriz Viral/administração & dosagem , Proteínas da Matriz Viral/genética , Imunidade nas Mucosas , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Pulmão/virologia , Pulmão/imunologia , Glicoproteínas/imunologia , Glicoproteínas/administração & dosagem , Administração através da Mucosa , Vírus Sinciciais Respiratórios/imunologia , Linfócitos T/imunologiaRESUMO
Inadvertent injection of drugs into the epidural space has a potential for serious morbidity and is probably underestimated and underreported. A 39-year-old female with no medical history presented for delivery. An epidural catheter was requested and correctly placed. Continuous epidural infusion was chosen for labor analgesia. Six hours after the parturient complained about inefficient analgesia, a syringe swap with insulin was identified. Despite the risk of possibly neurotoxic preservatives in the insulin formulation, no neurological sequelae were observed. This case highlights the issue of wrong-route drug administration and the urgent need to adopt route-specific connections.
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Minibus taxis, a form of informal shared mobility that carries up to 16 passengers, is the main mode of public transport in sub-Saharan Africa, and given global trends, a large-scale shift to electric paratransit is imminent in the coming decades. Modeling the energy consumption (kWh/km) of electric vehicle (EV) fleets is a pre-requisite for planning for fleet deployment, especially in energy-constrained contexts. Given the paucity of EVs in sub-Saharan Africa, ground-truth data on the energy consumption of electric paratransit does not exist for many developing contexts. Consequently, GPS tracking data on internal combustion engine (ICE) versions of these vehicles is often used to estimate the energy consumption of an electric equivalent. To date, only per-minute GPS tracking data has been captured on these vehicles and used for energy consumption estimates. But this sampling frequency is insufficient for accurate energy consumption estimates, especially given the unique micro-mobility patterns of minibus taxis that are characterized by many rapid acceleration/deceleration events in quick succession. Although simulators can be used to interpolate between the dataset, they have been shown to be inaccurate in the regional context. This article presents a dataset of high-fidelity micromobility data captured on minibus taxis in transit on four typical route types: inter-city, intra-city, uphill, and downhill. The main objective was to estimate energy requirements for the eventual electrification of these vehicles, the data was thus processed according to an electro-kinetic model. This high-fidelity mobility data was captured by "standardised passengers" with bespoke GPS-location logging devices sampling at 1 Hz. Trips on the four route types were recorded and saved in six folders - three routes, each in two directions, with one route being uphill in one direction and downhill in another. Each of the six folders have subfolders for time of day - morning, afternoon, and evening. In total 62 trips were recorded with varying durations, depending on the traffic and route length.
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The C-N coupling reaction demonstrates broad application in the fabrication of a wide range of high value-added organonitrogen molecules including fertilizers (e.g., urea), chemical feedstocks (e.g., amines, amides), and biomolecules (e.g., amino acids). The electrocatalytic C-N coupling pathways from waste resources like CO2, NO3-, or NO2- under mild conditions offer sustainable alternatives to the energy-intensive thermochemical processes. However, the complex multistep reaction routes and competing side reactions lead to significant challenges regarding low yield and poor selectivity toward large-scale practical production of target molecules. Among diverse catalyst systems that have been developed for electrochemical C-N coupling reactions, the atomically dispersed catalysts with well-defined active sites provide an ideal model platform for fundamental mechanism elucidation. More importantly, the intersite synergy between the active sites permits the enhanced reaction efficiency and selectivity toward target products. In this Review, we systematically assess the dominant reaction pathways of electrocatalytic C-N coupling reactions toward various products including urea, amines, amides, amino acids, and oximes. To guide the rational design of atomically dispersed catalysts, we identify four key stages in the overall reaction process and critically discuss the corresponding catalyst design principles, namely, retaining NOx/COx reactants on the catalyst surface, regulating the evolution pathway of N-/C- intermediates, promoting C-N coupling, and facilitating final hydrogenation steps. In addition, the advanced and effective theoretical simulation and characterization technologies are discussed. Finally, a series of remaining challenges and valuable future prospects are presented to advance rational catalyst design toward selective electrocatalytic synthesis of organonitrogen molecules.
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Epigenetic-mediated modifications, induced by adverse environmental conditions, significantly alter an organism's physiological mechanisms. Even after elimination of the stimulus, these epigenetic modifications can be inherited through mitosis, thereby triggering transgenerational epigenetics. Plastics, with their versatile properties, are indispensable in various aspects of daily life. However, due to mismanagement, plastics have become so ubiquitous in the environment that no ecosystem on Earth is free from micro-nanoplastics (MNPs). This situation has raised profound concerns regarding their potential impact on human health. Recently, both in vivo animal and in vitro human cellular models have shown the potential to identify the harmful effects of MNPs at the genome level. The emerging epigenetic impact of MNP exposure is characterized by short-term alterations in chromatin remodelling and miRNA modulation. However, to understand long-term epigenetic changes and potential transgenerational effects, substantial and more environmentally realistic exposure studies are needed. In the current review, the intricate epigenetic responses, including the NHL-2-EKL-1, NDK-1-KSR1/2, and WRT-3-ASP-2 cascades, wnt-signalling, and TGF- ß signalling, established in model organisms such as C. elegans, mice, and human cell lines upon exposure to MNPs, were systematically examined. This comprehensive analysis aimed to predict human pathways by identifying human homologs using databases and algorithms. We are confident that various parallel miRNA pathways, specifically the KSR-ERK-MAPK pathway, FOXO-Insulin cascade, and GPX3-HIF-α in humans, may be influenced by MNP exposure. This influence may lead to disruptions in key metabolic and immune pathways, including glucose balance, apoptosis, cell proliferation, and angiogenesis. Therefore, we believe that these genes and pathways could serve as potential biomarkers for future studies. Additionally, this review emphasizes the origin, dispersion, and distribution of plastics, providing valuable insights into the complex relationship between plastics and human health while elaborating on the epigenetic impacts.
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Biomarcadores , Epigênese Genética , Humanos , Epigênese Genética/efeitos dos fármacos , Biomarcadores/metabolismo , Animais , Microplásticos/toxicidade , MicroRNAs/genética , MicroRNAs/metabolismo , Nanopartículas/toxicidade , Plásticos/toxicidadeRESUMO
The use of allergen immunotherapy (AIT) in Brazil has specific regional conditions owing to the pattern of allergen sensitization, as well as to genetic, socioeconomic, and cultural characteristics. This review article aims to discuss the clinical practice of AIT by the subcutaneous or sublingual route in Brazil, addressing the possibilities of transition between these forms of administration. A systematic review using the PubMed and Cochrane databases was performed, and the websites of major allergy and immunology organizations were consulted. Knowledge of the mechanism of action of subcutaneous immunotherapy and sublingual immunotherapy, together with Brazilian real-life experience, allowed us to establish recommendations regarding switching routes of AIT administration in selected cases. Careful analysis of each clinical situation is necessary to perform the transition between subcutaneous and sublingual allergen immunotherapy.
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This study employs a Model Reduction Technique (MRT) to simplify the four-step catalytic carbon monoxide (CO) oxidation reaction. The C-matrix method identifies key elements, key/non key components, and key reactions, while the Intrinsic Low-Dimensional Manifold (ILDM) pinpoints a Slow-Invariant Manifold (SIM) important for understanding key species behavior. Sensitivity analysis can be considered for measuring the efficiency of the chemical species in detailed mechanism. This systematic approach contributes to optimizing and controlling complex reactions offering broad application potential. In addition to the mathematical proof, the validation of the given chemical model is rectified. The comparison between the slow invariant manifold of both reaction routes is reported and the computational based results performed in this study are obtained through MATLAB.
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Cerebrospinal fluid shunts are the primary treatment for hydrocephalus. However, prolonged external ventricular drain (EVD) use can lead to central nervous system (CNS) infections such as ventriculitis. In the ICU setting, nosocomial infections with gram-negative, multi-drug resistant (MDR) organisms such as Acinetobacter baumannii (AB) prevail, leading to poor outcomes. AB infections are notably challenging due to their genetic drug resistance. Colistin has been reintroduced for use against gram-negative MDR pathogens but has limitations in CNS penetration when administered intravenously. Therefore, intraventricular (IVT) or intrathecal administration of colistin is recommended to enhance its therapeutic reach within the CNS. We present a case of a 22-year-old male admitted after an electric scooter accident with head trauma and hydrocephalus. A ventriculoperitoneal (VP) shunt was inserted, complicated by a nosocomial neuroinfection. Empiric IV therapy with meropenem and vancomycin was initiated. The VP shunt culture identified AB susceptible only to colistin. Intravenous (IV) colistin was added to meropenem with no significant improvement. The addition of IVT colistin significantly improved the patient's neurological condition and reduced inflammatory markers. The patient experienced one myoclonic seizure during IVT colistin treatment, managed with antiepileptics. After multiple unrelated nosocomial complications, the patient was discharged in good condition to rehabilitation. This case suggests that IVT colistin, combined with IV administration, may be preferable over IV colistin alone. Medical staff should be informed about the correct prevention and care of EVD-associated infections.
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The honey bee, a significant crop pollinator, encounters pesticides through various routes of exposure during foraging and flower visitation. Considering the potential threat of pesticide poisoning, the indigenous Saudi bee Apis mellifera jemenitica is susceptible to the risks associated with acetamiprid, a neonicotinoid insecticide. This study investigates the acetamiprid-induced effects on the survival, olfactory learning, and memory formation of A. m. jemenitica through two exposure routes: topical application and oral ingestion. Field-realistic and serially diluted concentrations (100, 50, 25, and 10 ppm) of acetamiprid led to notable mortality at 4, 12, 24, and 48 h after treatment, with peak mortality observed at 24 h and 48 h for both exposure routes. Bee mortality was concentration-dependent, increasing with the rising concentration of acetamiprid at the tested time intervals. Food consumption following oral exposure exhibited a concentration-dependent pattern, steadily decreasing with increasing concentrations of acetamiprid. Oral exposure resulted in a substantially higher cumulative mortality (55%) compared to topical exposure (15%), indicating a significant disparity in bee mortality between the two exposure routes. The 24 h post-treatment LC50 values for acetamiprid were 160.33 and 12.76 ppm for topical application and oral ingestion, respectively. The sublethal concentrations (LC10, LC20, and LC30) of acetamiprid were 15.23, 34.18, and 61.20 ppm, respectively, following topical exposure, and 2.85, 4.77, and 6.91 ppm, respectively, following oral exposure. The sublethal concentrations of acetamiprid significantly decreased learning during the 2nd-3rd conditioning trials and impaired memory formation at 2, 12, and 24 h following both topical and oral exposure routes, compared to the control bees. Notably, the sublethal concentrations were equally effective in impairing bee learning and memory. Taken together, acetamiprid exposure adversely affected bee survival, hindered learning, and impaired the memory retention of learned tasks.
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The disadvantages of some conventional drugs, including their low bioavailability, poor targeting efficiency, and important side effects, have led to the rational design of drug delivery systems. In particular, the introduction of drug delivery systems is a potential approach to enhance the uptake of therapeutic agents and deliver them at the right time and in the right amount of concentration at the required site, as well as open new strategies for effective illness treatment. In this review, we provide a basic understanding of drug delivery systems with an emphasis on the use of cyclodextrin-, polymer- and surfactant-based delivery systems. These systems are very attractive because they are biocompatible and biodegradable nanomaterials with multifunctional components. We also provide some details on their design considerations and their use in a variety of medical applications by employing several routes of administration.
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Electrochemotherapy (ECT) combines the reversible electroporation (rEP) with intravenous (i.v.) or intratumoral (i.t.) administration of chemotherapeutic drugs. We conducted this study to compare the efficacy of i.v., i.t., and i.v. + i.t. injection of bleomycin (BLM) in ECT treatment of colorectal hepatic metastases in a rat model. WAG/Rij rats were randomized into three groups and underwent ECT with i.v., i.t., or i.v. + i.t. injection of BLM. Tumor volumes and oxygenation were measured by means of ultrasound and photoacoustic imaging. Moreover, liver and tumor tissue were analyzed by histology and immunohistochemistry. The i.v. and i.v. + i.t. groups exhibited a 44.0% and 46.6% reduction in oxygen saturation of the tumor tissue when compared to pretreatment values, whereas the i.t. group only showed a reduction of 35.2%. The extent of tumor tissue necrosis did not statistically differ between the groups. However, the i.t. group showed a tendency towards a lower necrosis rate. Cell proliferation, apoptotic cell death, vascularization, and immune cell infiltration were comparable in the treated tumors of the three groups. ECT with i.v. administration of BLM should be preferred in clinical practice, as the combined i.v. + i.t. therapy did not show superior oncological outcomes in the present study.