Meta-analysis unravels the complex combined toxicity of microplastics and antibiotics in aquatic ecosystems.

The aquatic ecosystem, a repository for various pollutants, has been identified as a crucial zone where microplastics (MPs) serve as vectors for antibiotics, facilitating their spread. Despite this, the influence of MPs on the toxicity of antibiotics remains a topic of debate. In this study, we conduct a global meta-analysis, examining 730 datasets from 29 laboratory studies. Our findings reveal that the impact of MPs on antibiotic toxicity is highly dependent on biological response pathways, microplastic concentration, antibiotic properties, and exposure time. We observed that MPs amplify the accumulation of antibiotics in aquatic organisms, significantly heightening their adverse effects on growth, development, and immune functions. Intriguingly, MPs appear to mitigate the reproductive toxicity caused by antibiotics. A notable inverse relationship was identified between antibiotic toxicity and microplastic concentration and exposure time. Furthermore, antibiotic concentration predominantly affects growth, development, and reproductive health, whereas exposure time is critical in determining antibiotic accumulation and immune-related toxicity. These insights underscore that microplastic co-exposure can modify the toxicological profile of antibiotics. The outcomes of this research enhance our comprehensive understanding of the intricate combined effects of MPs and antibiotics on aquatic life, emphasizing the necessity for informed scientific management of these emerging contaminants.

Biofilm enhances the interactive effects of microplastics and oxytetracycline on zebrafish intestine.

The enhanced adsorption of pollutants on biofilm-developed microplastics has been proved in many studies, but the ecotoxicological effects of biofilm-developed microplastics on organisms are still unclear. In this study, adult zebrafish were exposed to original microplastics, biofilm-developed microplastics, original microplastics absorbed with oxytetracycline (OTC), and biofilm-developed microplastics absorbed with OTC for 30 days. The intestinal histological damage, intestinal biomarker response, gut microbiome and antibiotic resistance genes (ARGs) profile of zebrafish were measured to explore the roles of biofilm in the effects of microplastics. The results showed that biofilm-developed microplastics significantly increased the number of goblet cells in intestinal epithelium compared with the control group. The biofilm-developed microplastics also induced the oxidative response in the zebrafish intestines, and biofilm changed the response mode in the combined treatment with OTC. Additionally, the biofilm-developed microplastics caused intestinal microbiome dysbiosis, and induced the abundance of some pathogenic genera increasing by several times compared with the control group and the original microplastics treatments, regardless of OTC adsorption. Furthermore, the abundance of ARGs in biofilm-developed microplastics increased significantly compared with the control and the original microplastic treatments. This study emphasized the significant influence and unique role of biofilm in microplastic studies.

Design, Synthesis, and Evaluation of [18F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1.

Compounds 8a-j were designed to adjust the mode of interaction and lipophilicity of FTT by scaffold hopping and changing the length of the alkoxy groups. Compounds 8a, 8d, 8g, and BIBD-300 were screened for high-affinity PARP-1 through enzyme inhibition assays and are worthy of further evaluation. PET imaging of MCF-7 subcutaneous tumors with moderate expression of PARP-1 showed that compared to [18F]FTT, [18F]8a, [18F]8d, and [18F]8g exhibited greater nonspecific uptake, a lower target-to-nontarget ratio, and severe defluorination, while [18F]BIBD-300 exhibited lower nonspecific uptake and a greater target-to-nontarget ratio. PET imaging of 22Rv1 subcutaneous tumors, which highly express PARP-1, confirmed that the uptake of [18F]BIBD-300 in normal organs, such as the liver, muscle, and bone, was lower than that of [18F]FTT, and the ratio of tumor-to-muscle and tumor-to-liver [18F]BIBD-300 was greater than that of [18F]FTT. The biodistribution results in mice with MCF-7 and 22Rv1 subcutaneous tumors further validated the results of PET imaging. Unlike [18F]FTT, which mainly relies on hepatobiliary clearance, [18F]BIBD-300, which has lower lipophilicity, undergoes a partial shift from hepatobiliary to renal clearance, providing the possibility for [18F]BIBD-300 to indicate liver cancer. The difference in the PET imaging results for [18F]FTT, [18F]BIBD-300, and [18F]8j in 22Rv1 mice and the corresponding molecular docking results further confirmed that subtle structural modifications in lipophilicity greatly optimize the properties of the tracer. Cell uptake experiments also demonstrated that [18F]BIBD-300 has a high affinity for PARP-1. Metabolized and unmetabolized [18F]FTT and [18F]BIBD-300 were detected in the brain, indicating that they could not accurately quantify the amount of PARP-1 in the brain. However, PET imaging of glioma showed that both [18F]FTT and [18F]BIBD-300 could accurately localize both in situ to C6 and U87MG tumors. Based on its potential advantages in the diagnosis of breast cancer, prostate cancer, and glioma, as well as liver cancer, [18F]BIBD-300 is a new option for an excellent PARP-1 tracer.

18F-Labeled PET Tracers Specific for Adenosine A2A Receptor: Design, Synthesis, and Biological Evaluation.

By modifying the structures of targeted A2AR antagonists and tracers, novel compounds 3, 7a, 9, 12c, and BIBD-399 were designed and synthesized. In vitro inhibition experiments demonstrated that 3, 12c, and BIBD-399 have high affinity for A2AR. [18F]3 and [18F]BIBD-399 were successfully synthesized. In terms of biological distribution, the brain uptake of [18F]MNI-444 exhibits greater than that of [18F]3 and [18F]BIBD-399. PET imaging shows that [18F]3 is off-target in the brain, while [18F]BIBD-399 and [18F]MNI-444 can be specifically imaged in regions with high A2AR expression. Differently, [18F]BIBD-399 could quickly reach equilibrium in the targeted region within 10 min after administration, while [18F]MNI-444 shows a slowly increasing trend within 2 h of administration. [18F]BIBD-399 is mainly metabolized by the liver and kidney, and there is no obvious defluorination in vivo. Additional in vitro autoradiography showed that the striatal signals of [18F]BIBD-399 and [18F]MNI-444 were inhibited by the A2AR antagonist SCH442416 but not by the A1R antagonist DPCPX, demonstrating the high A2AR binding specificity of [18F]BIBD-399. Molecular docking further confirms the high affinity of MNI-444 and BIBD-399 for A2AR. Further tMCAo imaging showed that [18F]BIBD-399 can sensitively distinguish between infarcted and noninfarcted sides, a capability not observed with [18F]MNI-444. Given its pharmacokinetic properties and the ability to identify lesion regions, [18F]BIBD-399 has potential advantages in monitoring A2AR changes, meriting further clinical investigation.

One-Dimensional Covalent Organic Framework-Based Multilevel Memristors for Neuromorphic Computing.

Memristors are essential components of neuromorphic systems that mimic the synaptic plasticity observed in biological neurons. In this study, a novel approach employing one-dimensional covalent organic framework (1D COF) films was explored to enhance the performance of memristors. The unique structural and electronic properties of two 1D COF films (COF-4,4'-methylenedianiline (MDA) and COF-4,4'-oxydianiline (ODA)) offer advantages for multilevel resistive switching, which is a key feature in neuromorphic computing applications. By further introducing a TiO2 layer on the COF-ODA film, a built-in electric field between the COF-TiO2 interfaces could be generated, demonstrating the feasibility of utilizing COFs as a platform for constructing memristors with tunable resistive states. The 1D nanochannels of these COF structures contributed to the efficient modulation of electrical conductance, enabling precise control over synaptic weights in neuromorphic circuits. This study also investigated the potential of these COF-based memristors to achieve energy-efficient and high-density memory devices.

Design of Novel 18F-Labeled Amino Acid Tracers Using Sulfur 18F-Fluoride Exchange Click Chemistry.

[18F]Gln-OSO2F, [18F]Arg-OSO2F, and [18F]FSY-OSO2F were designed by introducing sulfonyl 18F-fluoride onto glutamine, arginine, and tyrosine, respectively. [18F]FSY-OSO2F can be prepared directly by sulfur 18F-fluoride exchange, while [18F]Gln-OSO2F and [18F]Arg-OSO2F require a two-step labeling method. Those tracers retain their typical transport characteristics for unmodified amino acids. Both PET imaging and biodistribution confirmed that [18F]FSY-OSO2F visualized MCF-7 and 22Rv1 subcutaneous tumors with high contrast, and its tumor-to-muscle ratio was better than that of [18F]FET. However, [18F]Gln-OSO2F and [18F]Arg-OSO2F poorly image MCF-7 subcutaneous tumors, possibly due to differences in the types and amounts of transporters expressed in tumors. All three tracers can visualize the U87MG glioma. According to our biological evaluation, none of the tracers evaluated in this study exhibited obvious defluorination, and subtle structural changes led to different imaging characteristics, indicating that the application of sulfur 18F-fluoride exchange click chemistry in the design of radioactive sulfonyl fluoride amino acids is feasible and offers significant advantages.

Removal of sulfonamides from water by wetland plants: Performance, microbial response and mechanism.

Sulfonamides are widely used in the clinical and animal husbandry industry because of their antibacterial properties and low cost. However, Sulfonamides cannot be fully absorbed by human bodies or animals, 50 %-90 % will be discharged from the bodies, and enter waters and soils through a variety of ways, causing environmental harm. Phytoremediation as a green in situ repair technology has been proven effective in sulfonamides removal, but the underlying mechanisms are still a question that needs to be further studied. In order to explore the relationship between SAs removal and plants (S. validus), root exudates secreted from plants, and microorganisms, the study conducted a series of experiments and used the structural equation model to quantify the pathways of sulfonamides removal in wetland plants. The removal rate of sulfonamides in the plant treatment group (77.6-92 %) was significantly higher than that in the root exudate treatment group (25.7-36.3 %) and water treatment group (16.3-19.6 %). Plant uptake (λ1 = 0.72-0.77) and microbial degradation (λ2 = 0.31-0.38) were the most important pathways for sulfonamides removal. Sulfonamides could be directly removed through the accumulation, adsorption and metabolism of plants. Meanwhile, plants could indirectly remove sulfonamides by promoting microbial degradation. These results will facilitate our understanding of the underlying mechanism and the improvement of sulfonamides removal efficiency in phytoremediation.

Influence of extracellular polymeric substances on arsenic bioaccumulation and biotransformation in biofilms.

It is well recognized that biofilms can biosorb and biotransform heavy metals in aquatic environments. However, the effects of extracellular polymeric substance (EPS) on inorganic arsenic (As) bioaccumulation and biotransformation in biofilms are still unrevealed and need to be investigated. In order to explore the above scientific issues, the As accumulation and speciation in EPS-containing or EPS-free biofilms and growth medium under As(V)/As(III) exposure conditions were measured. After the removal of EPS, the amount of As uptake (Asup) and As adsorption (Asad) in biofilms were significantly reduced, no matter whether exposed to As(V) or As(III). FTIR analysis further suggested that the interaction between these functional groups with As was limited after the removal of EPS. In the EPS-containing biofilms, the Asad was mainly As(V) with low toxicity. However, after the removal of EPS, the Asad was mainly As(III) with high fluidity, and no methylated As was found. Moreover, the removal of EPS inhibited As(III) oxidation and methylation by biofilms, resulting in the decrease of As(V) and methylated As in the growth medium. The findings of this study emphasized the essential impact of EPS on the biosorption and biotransformation of As in biofilms. This study provides a unique understanding of the role of biofilms in As biogeochemical cycle, and water quality purification function in water environments.

How antibiotic exposure affect predator-prey interactions by population dynamics in ciliates?

Biodiversity loss resulting from environmental pollution is a global concern. While interspecific interactions are central to ecology, the impact of environmental pollution on predator-prey interactions and its ecological consequences, such as extinction and biodiversity loss, remain unclear. To investigate the effects of antibiotic exposure on predation strength and the resulting ecological consequence, the Didinium-Paramecium was utilized as a predator-prey model and exposed to nitrofurazone or erythromycin, two common pollutants, respectively. Initially, we determined prey population growth dynamics, body size, and predator numerical-functional responses. Subsequently, these above parameters were integrated into a mathematical model of predator-prey predation. Then both the long time-series data and phase portraits obtained through model simulation were used to estimate interaction strength and to predict the outcome of predator-prey coexistence. Our results revealed that exposure to either antibiotic significantly reduced prey population growth parameters (e.g., µmax and K) while increasing individual body size. The combined effects of antibiotic exposure and predation pressure on population growth inhibition or body size promotion were variable, mostly additive, with a few cases of synergy and extremely rare antagonism, depending on antibiotic exposure concentration. As antibiotic exposure concentration increased, the predator rmax generally declined, while functional responses varied depending on specific parameters, implying a decrease in predator-prey interaction strength. Analyses of phase portrait features showed that the population oscillation amplitude decreased with increasing antibiotic exposure concentrations, the cycle length of adjacent peaks increased, and prey extinction occurred earlier. In conclusion, antibiotic exposure reduced both predator and prey fitness, underlying the reason antibiotics reduces the strength of predator-prey interaction. Despite the indirect benefits of prey gain from this, the presence of predators can expedite the process of prey extinction caused by antibiotic exposure.

Design, Synthesis, and Evaluation of 18F-Labeled Tracers Targeting Fibroblast Activation Protein for Brain Imaging.

Fibroblast activation protein (FAP) is closely related to central nervous system diseases such as stroke and brain tumors, but PET tracers that can be used for brain imaging have not been reported. Here, we designed, synthesized, and evaluated 18F-labeled UAMC1110 derivatives suitable for brain imaging targeting FAP. By substituting the F atom for the H atom on the aromatic ring of compound UAMC1110, 1a-c were designed and prepared. 1a-c were confirmed to have a high affinity for FAP through molecular docking and enzyme assay. [18F]1a-c were successfully prepared and confirmed to have high affinity. The stability in vivo indicates that no obvious metabolites of [18F]1a,b were found in the plasma 1 h after injection, which is beneficial for brain imaging. In vitro cell uptake experiments showed that [18F]1a,b and [68Ga]FAPI04 exhibited similar uptake and internalization rates. PET imaging of U87MG subcutaneous tumor showed that [18F]1a,b could penetrate the blood-brain barrier with higher uptake and longer retention time than [68Ga]FAPI04 (uptake at 62.5 min, 1.06 ± 0.23, 1.09 ± 0.25% ID/g vs 0.21 ± 0.10% ID/g, respectively). The brain-to-blood ratios of [18F]1a,b were better than [68Ga]FAPI04. Biodistribution and PET imaging showed that [18F]1a had better uptake on tumors and a higher tumor-to-muscle ratio than [18F]1b and [68Ga]FAPI04. Further imaging of U87MG intracranial glioma showed that [18F]1a outlined high-contrast gliomas in a short period of time compared to [18F]1b. Therefore, [18F]1a is expected to be useful in the diagnosis of FAP-related brain diseases.

Unevenly distributed CO2 and its impacts on terrestrial carbon uptake under the changing land uses.

Changes in land-use structure and pattern can affect both atmospheric CO2 concentrations and the terrestrial carbon budget. To explore the effects of non-uniformly distributed CO2 concentration on terrestrial carbon uptake under land-use changes, this study integrated global CO2 concentrations, Net Primary Productivity (NPP), and land-use data under historical period and SSP1-2.6, SSP2-4.5 and SSP5-8.5 scenarios from 1850 to 2100. Land-use intensity (LUI) and the CO2 correlation to NPP were calculated using partial correlation analysis by controlling LUI. The results showed that NPP growth over the forest was the highest among the land-use types, reaching 0.54 g C·m2, 2.06 g C·m2 and 4.64 g C·m2, respectively, under SSP1-2.6, SSP2-4.5, and SSP5-8.5 scenarios. Among all the scenarios, the average correlation levels of atmospheric CO2 and NPP considering the LUI effect and controlling LUI ranged respectively from 0.34 to 0.68 and from 0.32 to 0.61 at a 5 % level of significance. It suggested that sensible land use planning might enhance the CO2 fertilization effect and that rises in CO2 concentrations could stimulate terrestrial carbon absorption. The findings add to the body of knowledge about the effects of atmospheric CO2 on terrestrial carbon uptake and serve as a scientific guide for protecting terrestrial carbon stocks and managing land use.

DMNet: A Personalized Risk Assessment Framework for Elderly People With Type 2 Diabetes.

Type 2 diabetes is the most common chronic disease for the elderly people. This disease is difficult to be cured and causes continued medical expenses. The early and personalized risk assessment of type 2 diabetes is necessary. So far, various type 2 diabetes risk prediction methods have been proposed. However, these methods have three major issues: 1) not fully considering the importance of personal information and rating information of healthcare system, 2) not adopting the long-term temporal information, and 3) not comprehensively capturing the correlation between the diabetes risk factor categories. To address these issues, the personalized risk assessment framework for elderly people with type 2 diabetes is needed. However, it is very challenging due to two reasons, namely imbalanced label distribution and high-dimensional features. In this paper, we propose diabetes mellitus network framework (DMNet) for type 2 diabetes risk assessment of elderly people. Specifically, we propose tandem long short-term memory to extract the long-term temporal information of different diabetes risk categories. In addition, the tandem mechanism is used to capture the correlation between the diabetes risk factor categories. To balance the label distribution, we adopt the method of synthetic minority over-sampling technique with Tomek links. To form the better feature representations, we utilize entity embedding to solve the problem of high-dimensional features. To evaluate the performance of our proposed method, we conduct the experiments on a real-world dataset called Research on Early Life and Aging Trends and Effects. The experiment results show that DMNet outperforms the baseline methods in terms of six evaluation metrics (i.e., accuracy of 0.94, balanced accuracy of 0.94, precision of 0.95, F1-score of 0.95, recall of 0.95 and AUC of 0.94).

Synthesis and In Vitro and In Vivo Evaluation of 18F-Labeled Positron Emission Tomography Tracers for Imaging Aß Plaques.

Accurate quantification of amyloid beta (Aß) plaques is an important indicator for Alzheimer's disease diagnosis and treatment. For this purpose, new highly sensitive Aß tracers were designed by regulating the position and number of nitrogen atoms. A series of derivatives of florbetapir (AV45) containing different numbers and positions of N atoms were synthesized and evaluated for in vitro affinity and in vivo biodistribution. Preliminary study results showed that [18F]BIBD-124 and [18F]BIBD-127 had better clearance rates and less in vivo defluorination than AV45 in ICR (ICR = Institute of Cancer Research) mice. Autoradiography and molecular docking indicated that the binding sites of [18F]BIBD-124/127 were similar to that of [18F]AV45. Micro-positron emission tomography-computed tomography imaging further demonstrated that [18F]BIBD-124 could monitor Aß plaques similar to [18F]AV45. Besides, the imaging contrast of [18F]BIBD-124 is better than that of [18F]AV45. Mass spectrometric metabolic analysis showed that BIBD-124 was less demethylated than AV45 without subsequent acetylation, which might explain its less non-specific uptake and higher imaging contrast. Gauss calculations further confirmed that the introduction of N5 in [18F]BIBD-124 decreased demethylation. Considering imaging contrast and in vivo defluorination, [18F]BIBD-124 is expected to be a promising radiotracer of Aß plaques for further clinical trials.

Predation risk affects the ecotoxicity evaluation of antibiotics: Population growth and antioxidase activity in the ciliate Paramecium jenningsi.

Although predation risk exists under natural conditions, its role is usually ignored when evaluating the ecotoxicity of environmental contaminants, and the interaction between predation risk and antibiotic ecotoxicity is not yet clear. To investigate the nonconsumptive effects (NCEs) of predation on the ecotoxicity evaluation of antibiotics, the median lethal concentration (LC50), relative population growth rate (RGR), and activities of three antioxidases were measured in the ciliate Paramecium jenningsi exposed to graded concentrations of the antibiotics nitrofurazone (NFZ) or erythromycin (ERY) in the presence or absence of a predator, i.e., the ciliate Didinium nasutum. The results showed that (1) NCEs significantly reduced the LC50 of NFZ but had no effect on that of ERY; (2) predation pressure alone had no significant effect on the inhibitory rate of the P. jenningsi population, but the interaction with NFZ was synergistic, while that with CRY was additive; (3) the concentrationresponse (i.e., mortality) model for each antibiotic exposure with and without predation pressure differed significantly in the parameter slope; (4) RGRs were significantly reduced by antibiotic exposure or NCEs; only in NFZ-exposed groups did the RGRs decrease linearly with increasing exposure concentration; and (5) the activities of all three antioxidases significantly increased due to NCEs or following exposure to antibiotics. In brief, NCEs were detected in P. jenningsi, and these had additive or synergistic effects on antibiotic ecotoxicity, but their magnitude depended on the properties and exposure concentrations of the antibiotics. Our findings suggest that it is necessary to consider the roles of NCEs in the ecotoxicity evaluation of environmental contaminants.

Influencing factors of antibiotic resistance genes removal in constructed wetlands: A meta-analysis assisted by multivariate statistical methods.

In order to control antibiotic resistance genes (ARGs) diffusion in constructed wetlands, it is critical to explore the main factors influencing ARGs removal and understand its mechanism. Despite the fact that numerous studies have been conducted to determine the factors influencing ARGs removal by constructed wetlands in recent years, attempts to use published data and incorporate them into a comprehensive comparison and analysis are still limited. A framework for literature collection, data extraction and statistical analysis (LDS) was constructed in this study. The main factors influencing antibiotics and ARGs removal by constructed wetlands were identified using this framework. The results showed that nutrients, types of constructed wetlands and hydraulic loading were the principal factors influencing the removal of most antibiotics. The principal factors influencing the most ARGs removal were mobile genetic elements, plants, volume of constructed wetlands and running time. After purification by constructed wetlands, the risk coefficient of antibiotics decreased significantly, while the relative abundance of most ARGs did not change significantly. The analysis results of linear mixed model showed that the relationship between antibiotics and ARGs in effluent was closer than that in influent. LDS framework provides a new platform for the study of influencing factors of pollutant removal based on data mining.

Accumulation and ecotoxicological effects induced by combined exposure of different sized polyethylene microplastics and oxytetracycline in zebrafish.

Microplastics have been widely reported as carriers of antibiotics, yet studies investigating the combined ecotoxicology of microplastics and antibiotics on organisms is limited. In this study, different sized polystyrene plastics and oxytetracycline (OTC) were used to carry out a 30-day single and binary-combined exposure experiment of zebrafish, and the microplastics and OTC accumulation, liver histological alteration, biomarkers and transcriptomic response of zebrafish were evaluated. Our results indicated that 300 nm and 50 nm plastic particles increased the OTC accumulation in liver by 33.8% and 44.5%, respectively. Microplastics and OTC induced severe liver histological damage, and the damage is size-dependent, increasing with the decrease of microplastics sizes. The liver biomarkers indicated a different response pattern in single microplastics exposure and combined with OTC, single or co-exposure of 50 nm nano-plastics and OTC induced intense responses of integrated biomarker response values. The 50 nm nano-plastics, OTC and their combined exposure induced 1330, 2693 and 3965 significantly differentially expressed genes, respectively, in which the steroid biosynthesis pathway was significantly affected by all the three treatments. This study elucidated the size-dependent effects of microplastics and provided detailed data from histopathology to transcriptome profile, enhancing our understanding of the ecotoxicity of microplastics and OTC.

Food, Energy, and Water Nexus at Household Level: Do Sustainable Household Consumption Practices Promote Cleaner Environment?

Governments around the globe are trying to find sustainable solutions for lessening pressure on natural resources and reducing carbon emissions. Daily household consumption of food, energy, and water has an impact on stocks of natural resources, environmental quality, and climate change. Households have significant potential for increasing conservation actions for efficient use of natural resources and greenhouse gas emissions. Households could contribute to a clean and healthy environment by adopting sustainable household practices through lower per capita consumption and carbon emissions. This study explored the role of different sustainable household consumption practices in promoting a clean environment as well as the factors affecting the adoption of these practices in Pakistan. Factor analysis and an ordered probit model were used to analyze the data from 1424 participants chosen through a multistage random sampling technique. The factor analysis identified 35 sustainable household practices for sustainable consumption. These 35 practices were grouped into the underlying factors of "Food" (14 items), "Energy" (12 items), and "Water" (9 items). The results from the econometric model showed a significant relationship between gender, education, residential area, family size, and income and the adoption of sustainable household consumption practices. Statistically, higher levels of reported sustainable consumption practices were apparent among females, households living in urban areas, more educated people, individuals of large family sizes, and more affluent households. Therefore, public policies for taking care of the environment need to put households at the center while at the same time promoting mass uptake of sustainable consumption practices related to food, energy, and water. In addition, the sector-specific policies also need to be augmented through focus on household-level consumption and production dynamics for achieving the UN's SDGs.

Combined effects of micro-/nano-plastics and oxytetracycline on the intestinal histopathology and microbiome in zebrafish (Danio rerio).

Accumulated evidence has demonstrated that microplastics and oxytetracycline (OTC) affect organisms, but few studies have investigated their combined effects on aquatic organisms. In this study, adult zebrafish (Danio rerio) were exposed to single and binary-combined contamination of micro-, nano-sized polystyrene plastics and OTC for 30 days, and the intestinal histopathology, gut microbiota and antibiotic resistance genes (ARGs) of zebrafish were measured. The results showed that the intestinal epithelial damage increase with the decrease of plastic sizes. Nano-sized plastics, OTC and their combined exposure caused intestinal epithelial damage, and co-exposure with micro-sized plastics reduced the intestinal damage caused by single OTC exposure. The gut microbial communities were affected by the combined exposure to microplastics and OTC. Compared with the blank control, the relative abundance of Fusobacteria increased 12.7 % and 21.1 % in OTC combined with 45-85 µm micro-plastics (MOTC) and 40-54 nm nano-plastics (NOTC), respectively, and that of Bacteroidetes increased 26.2 % and 18.6 % in the MOTC and NOTC treatments, respectively. The effects of MOTC and NOTC on the biodiversity of the zebrafish gut microbiome were different; MOTC increased the biodiversity by 11.3 % compared with the blank control, whereas NOTC decreased the biodiversity by 8.8 % compared with the blank control. Furthermore, the abundance of ARGs in 40-54 nm nano-plastics, MOTC and NOTC treatments was increased 96.9 %, 96.6 % and 68.8 % compared with the control group, respectively. Additionally, significant differences were observed in ARGs characteristics between the micro- and nano-plastics treated groups whether combined with OTC or not. These results are essential to further understand the combined ecotoxicological effects of micro- or nano-plastics and antibiotics on aquatic organisms.

[18F]BIBD-239: 18F-Labeled ER176, a Positron Emission Tomography Tracer Specific for the Translocator Protein.

[11C]ER176 has adequate sensitivity to image the human brain translocator protein (TSPO) in all three genotypes by positron emission tomography (PET). However, its clinical application is limited by the short half-life of 11C (20.38 min). To overcome the deficiency of [11C]ER176 and keep the pharmacophore features of ER176 to the maximum extent, we designed four fluorine-labeled ER176 derivatives using the deuterium method. In vitro competition binding confirmed that the designed compounds had high affinity for TSPO. Biodistribution experiments showed that tissues with high expression of TSPO had high uptake of these compounds, as well as that the compound showed high brain penetration and mild defluorination in vivo. Therefore, [18F]BIBD-239 with simple synthesis conditions was selected for further biological evaluation. Theoretical simulations showed that BIBD-239 and ER176 have similar binding modes and sites to Ala147-TSPO and Thr147-TSPO, which indicated that the tracers may have consistent sensitivity to the three affinity genotypes. In vitro autoradiography and in vivo PET studies of the ischemic rat brain showed dramatically higher uptake of [18F]BIBD-239 on the lesion site compared to the contralateral side with good brain kinetics. Additionally, [18F]BIBD-239 provided clear tumor PET images in a GL261 glioma model. Importantly, PET imaging and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) results showed that in vivo defluorination and other metabolites of [18F]BIBD-239 did not interfere with brain imaging. Conclusively, [18F]BIBD-239, similar to ER176 with low polymorphism sensitivity, has simple labeling conditions, high labeling yield, high affinity, and high specificity for TSPO, and it is planned for further evaluation in higher species.

Novel 18F-Labeled PET Tracers Specific to Aromatase: Design, Synthesis, and Biological Evaluation.

The abnormal expression of aromatase is associated with the occurrence and development of a variety of neurological diseases and tumors. A series of 18F-labeled and 68Ga-labeled potential aromatase-binding candidate compounds were designed and synthesized based on the structures of aromatase inhibitors. Competitive inhibition experiments in vitro and molecular docking showed that BIBD-069 and BIBD-071 have high affinity for aromatase. The radiolabeling conditions of [18F]BIBD-069 and [18F]BIBD-071 were simple, and the yields were high. Biodistribution and in vivo inhibition experiments confirmed that [18F]BIBD-069 and [18F]BIBD-071 specifically bind to aromatase. [18F]BIBD-069 and [18F]BIBD-071 selectively imaged the amygdala and nucleus of the stria terminalis, which is similar to the imaging result of [11C]vorozole. Radiometabolites of [18F]BIBD-069 and [18F]BIBD-071 did not bind to aromatase and interfered with brain imaging. MicroPET-CT imaging further confirmed that [18F]BIBD-069 and [18F]BIBD-071 can specifically bind to aromatase and were not defluorinated in vivo. Given that [18F]BIBD-069 and [18F]BIBD-071 exhibit excellent aromatase binding affinities, mild radiolabeling conditions, and good pharmacokinetics, they can be important tools for the diagnosis and treatment of aromatase-related diseases.