Prohibitin 2 deficiency in photoreceptors leads to progressive retinal degeneration and facilitated Müller glia engulfing microglia debris.

Müller glia and microglia are capable of phagocytosing fragments of retinal cells in response to retinal injury or degeneration. However, the direct evidence for their mutual interactions between Müller glia and microglia in the progression of retinal degeneration (RD) remains largely unclear. This study aims to construct a progressive RD mouse model and investigate the activated pattern of Müller glia and the interplay between Müller glia and microglia in the early stage or progression of RD. A Prohibitin 2 (Phb2) photoreceptor-specific knockout (RKO) mouse model was generated by crossing Phb2flox/flox mice with Rhodopsin-Cre mice. Optical Coherence Tomography (OCT), histological staining, and Electroretinography (ERG) assessed retinal structure and function, and RKO mice exhibited progressive RD from six weeks of age. In detail, six-week-old RKO mice showed no significant retinal impairment, but severe vision dysfunction and retina thinning were shown in ten-week-old RKO mice. Furthermore, RKO mice were sensitive to Light Damage (LD) and showed severe RD at an early age after light exposure. Bulk retina RNA-seq analysis from six-week-old control (Ctrl) and RKO mice showed reactive retinal glia in RKO mice. The activated pattern of Müller glia and the interplay between Müller glia and microglia was visualized by immunohistology and 3D reconstruction. In six-week-old RKO mice or light-exposed Ctrl mice, Müller glia were initially activated at the edge of the retina. Moreover, in ten-week-old RKO mice or light-exposed six-week-old RKO mice with severe photoreceptor degeneration, abundant Müller glia were activated across the whole retinas. With the progression of RD, phagocytosis of microglia debris by activated Müller glia were remarkably increased. Altogether, our study establishes a Phb2 photoreceptor-specific knockout mouse model, which is a novel mouse model of RD and can well demonstrate the phenotype of progressive RD. We also report that Müller glia in the peripheral retina is more sensitive to the early damage of photoreceptors. Our study provides more direct evidence for Müller glia engulfing microglia debris in the progression of RD due to photoreceptor Phb2 deficiency.

Effect of denosumab on glucose metabolism in postmenopausal osteoporotic women with prediabetes: a study protocol for a 12-month multicenter, open-label, randomized controlled trial.

BACKGROUND: Participants with prediabetes are at a high risk of developing type 2 diabetes (T2D). Recent studies have suggested that blocking the receptor activator of nuclear factor-κB ligand (RANKL) may improve glucose metabolism and delay the development of T2D. However, the effect of denosumab, a fully human monoclonal antibody that inhibits RANKL, on glycemic parameters in the prediabetes population is uncertain. We aim to examine the effect of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes. METHODS: This is a 12-month multicenter, open-label, randomized controlled trial involving postmenopausal women who have been diagnosed with both osteoporosis and prediabetes. Osteoporosis is defined by the World Health Organization (WHO) as a bone mineral density T score of ≤ - 2.5, as measured by dual-energy X-ray absorptiometry (DXA). Prediabetes is defined as (i) a fasting plasma glucose level of 100-125 mg/dL, (ii) a 2-hour plasma glucose level of 140-199 mg/dL, or (iii) a glycosylated hemoglobin A1c (HbA1c) level of 5.7-6.4%. A total of 346 eligible subjects will be randomly assigned in a 1:1 ratio to receive either subcutaneous denosumab 60 mg every 6 months or oral alendronate 70 mg every week for 12 months. The primary outcome is the change in HbA1c levels from baseline to 12 months. Secondary outcomes include changes in fasting and 2-hour blood glucose levels, serum insulin levels, C-peptide levels, and insulin sensitivity from baseline to 12 months, and the incidence of T2D at the end of the study. Follow-up visits will be scheduled at 3, 6, 9, and 12 months. DISCUSSION: This study aims to provide evidence on the efficacy of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes. The results derived from this clinical trial may provide insight into the potential of denosumab in preventing T2D in high-risk populations. TRIAL REGISTRATION: This study had been registered in the Chinese Clinical Trials Registry. REGISTRATION NUMBER: ChiCTR2300070789 on April 23, 2023. https://www.chictr.org.cn .

Development of the Chronic Pain Cognition Scale: A Culture-Sensitive Pain Measurement in Chinese.

Purpose: People with pain problems are highly vulnerable to cultural disparities, and it is imperative to reduce these inequalities. This cross-sectional study aimed to develop a culturally sensitive Chronic Pain Cognition Scale (CPCS) for Chinese-/Chinese dialect-speaking populations and investigate its psychometric properties. Patients and Methods: Adult patients with chronic low back pain or chronic neck pain who visited pain clinics at a medical center in northern Taiwan were enrolled. Participants completed the demographic, intensity of pain, and two other related sensations, "Sng ()" and "Ma ()", often reported in Chinese-speaking populations, CPCS, Chronic Pain Acceptance Questionnaire-8, and Pain Self-Efficacy Questionnaire. Results: 200 patients were included. Patients' mean age was 64.84 ± 14.33, 126 (63.0%) were female, and 83 (41.5%) had 13+ years of education. The average duration of pain was 77.25 ± 97.46 months, the intensity of pain was 6.04 ± 2.50, Ma was 3.43 ± 3.24, and Sng was 4.54 ± 3.14. The CPCS comprised four factors: pain impact (how pain impact one's life), losing face (how one being disrespected due to pain), helplessness, and avoidance, with good structural validity and adequate reliability (Cronbach α, 0.60-0.81) and satisfactory criterion-related validity. Moreover, losing face, an essential concept in Chinese relationalism, was significantly related to pain, Sng, and Ma (r = 0.19, 0.15 and 0.16), but not to pain acceptance or self-efficacy, indicating a culturally specific element in pain measurement. Conclusion: The CPCS has good psychometric properties and is suitable for evaluating chronic pain in the clinical setting, and might be generalizable to other Chinese-/Chinese dialect-speaking populations.

Human-Guided Reinforcement Learning With Sim-to-Real Transfer for Autonomous Navigation.

Reinforcement learning (RL) is a promising approach in unmanned ground vehicles (UGVs) applications, but limited computing resource makes it challenging to deploy a well-behaved RL strategy with sophisticated neural networks. Meanwhile, the training of RL on navigation tasks is difficult, which requires a carefully-designed reward function and a large number of interactions, yet RL navigation can still fail due to many corner cases. This shows the limited intelligence of current RL methods, thereby prompting us to rethink combining RL with human intelligence. In this paper, a human-guided RL framework is proposed to improve RL performance both during learning in the simulator and deployment in the real world. The framework allows humans to intervene in RL's control progress and provide demonstrations as needed, thereby improving RL's capabilities. An innovative human-guided RL algorithm is proposed that utilizes a series of mechanisms to improve the effectiveness of human guidance, including human-guided learning objective, prioritized human experience replay, and human intervention-based reward shaping. Our RL method is trained in simulation and then transferred to the real world, and we develop a denoised representation for domain adaptation to mitigate the simulation-to-real gap. Our method is validated through simulations and real-world experiments to navigate UGVs in diverse and dynamic environments based only on tiny neural networks and image inputs. Our method performs better in goal-reaching and safety than existing learning- and model-based navigation approaches and is robust to changes in input features and ego kinetics. Furthermore, our method allows small-scale human demonstrations to be used to improve the trained RL agent and learn expected behaviors online.

Acute toxicity of tire wear particles and leachate to Daphnia magna.

Tire wear particles (TWP) are a new pollutant widely present in the environment, and have been identified as microplastics (MPs), which are receiving increasing attention due to their toxic effects on aquatic organisms. In this study, D. magna was used as test organism, and the leachate from TWP was prepared by hot water extraction for 30 (30-E) and 120 min (120-E). The acute toxic effects of particles and leachate on D. magna were studied under different exposure concentrations. The results showed that zinc and pyrene were the highest detected contaminants in the leachate. The 48 h-LC50 values for particles and leachate were determined to be 56.99, 461.30 (30-E), and 153.00 mg/L (120-E), respectively. Following a 48 h exposure period, the immobilization of D. magna exposed to the particles and their leachate were increased with the concentration increase. The physical damage of the gut was found to be a possible mechanism for particle-induced biotoxicity. The compounds leached from TWP were responsible for the acute toxicity of leachate. Particles usually demonstrated a greater degree of toxicity in comparison to their leachate, especially at environmentally relevant concentrations. Exposure to particles and leachate resulted in the inhibition of swimming speed, swimming acceleration, filtration rate, and ingestion rate in D. magna. Furthermore, thoracic limb activity was observed to be inhibited. The heart rate of D. magna was significantly increased by the presence of particles at a concentration of 200 mg/L and leachate at concentrations of 400 and 800 mg/L (120-E). The observed alterations in behavior and physiological endpoints may be related to oxidative stress and neurotoxicity in the organism. Reduced superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities indicated that D. magna may suffer from excessive oxidative stress, whereas the increase of acetylcholinesterase (AChE) activity may serve as a biomarker of susceptibility to evaluate the environmental risks of TWP and corresponding leachates as potential aquatic pollutants.. Therefore, a more comprehensive risk assessment of TWP in the environment is necessary.

Tissue-specific accumulation, depuration, and effects of perfluorooctanoic acid on fish: Influences of aqueous pH and sex.

Perfluorooctanoic acid (PFOA) is widely distributed in nature, particularly in aquatic environments. Its bioaccumulation and toxicity in aquatic organisms can be affected by both the chemical status of PFOA in water and the physiology of the organism. However, research on the patterns of these effects is scarce. In this study, we investigated the influence of aqueous pH (pH 6, acidic; pH 7.5, neutral; pH 9, basic) and fish sex on PFOA uptake, clearance, and biochemical effects in crucian carp (C. auratus) using flow-through exposure. In the 17-d kinetic experiment, PFOA bioaccumulation adhered to a uniform first-order model in which PFOA uptake rates from water to blood and liver in acidic conditions were faster than those in other conditions, indicating possible acidic pH influence on PFOA uptake. PFOA clearance rates in these compartments of males were slower than in females, which was attributed to the notably stronger expression of Oat2 (organic anion transporter 2, responsible for reabsorption) in the kidneys of males. Similar responses were observed for peroxisome proliferation-related biomarkers at different pH levels and in different sexes. These biochemical responses were driven by the internal concentrations of PFOA. The inhibition acetylcholinesterase activity in the fish brain was closely linked to changes in P-glycoprotein content, demonstrating a protective relationship. Collectively, an aqueous pH lower than 7.5 might affect the uptake of PFOA by fish. The clearance discrepancies between the sexes highlight the importance of anion carriers for ionizable organic compounds in aquatic organisms.

Cesium lead iodide electrospun fibrous membranes for white light-emitting diodes.

Inorganic perovskite cesium lead iodide nanocrystals (CsPbI3NCs) are good candidates for optoelectronic devices because of their excellent properties of remarkable luminous performance (high luminous efficiency, narrow luminous spectral line), and high photoelectric conversion efficiency by using simple preparation method. But their inherent poor stability greatly limits its practical applications. In this paper, electrospinning is used to grow fibrous membranes with embedded cesium lead iodide perovskite nanocrystals (PNCs) formedin situin a one-step process. It was found that cubicα-CsPbI3PNCs were formed in polymer fibers, showing bright and uniform fluorescence signals. Furthermore, the water wetting angles were increased by the fibrous structure enhancing the hydrophobicity and the stability of the fibrous membranes in water. The electrospun fibrous membrane containing CsPbI3was combined with another membrane containing CsPbBr3under a blue light-emitting diode (LED) to create a white LED (WLED) in air successfully with CIE coordinates (0.3020, 0.3029), and a correlated color temperature of 7527 °K, indicating high purity of WLED. Our approach provides a new way to create highly stable, photoluminescent water-resistant perovskite nanocrystalline films.

Intergenerational and biological effects of roxithromycin and polystyrene microplastics to Daphnia magna.

The influence of microplastics (MPs) on transgenerational effects of pharmaceuticals are drawing growing attention, however, whether aged process will alter the carrier effects of MPs were unknown. In this study, the intergenerational toxicity of single and combined exposure of polystyrene microplastics (PS-MPs) and roxithromycin (ROX) were investigated at the environmentally related concentrations, using Daphina magna as test organism. In the presence of UV-aged PS-MPs, the survival of D. magna for maternal generation (F0) at ROX concentration of 0.1 and 10 µg/L were increased by 20% and 40%, respectively. Meanwhile, the inhibition effects of ROX on the number of offspring and intrinsic rate of natural increase were obviously moderated. All these reproductive toxicity of ROX and PS-MPs in the first offspring (F1) were further aggravated both for the single and combined exposure. And the adverse effects disappeared much easier for the single exposure compared to the co-exposure through subsequent recovery. The combined exposure resulted in the change of inhibition of ROX on the swimming velocity and acceleration of D. magna into induction, while the feeding behavior kept inhibited. The AChE activity was distinctly increased by 1.61-3.25 times for the single and combined treatments, and the induction level of UV-aged MPs was higher than that of original MPs. Oxidative stress of the single exposure of ROX and original PS-MPs was observed with obvious induction of T-AOC and SOD activity, while the significant increase of MDA content was observed for the co-exposure. Among all indicators, the biochemical biomarkers and time of first brood were attributed to a class among all indicators, indicating that the time of first brood might be the most sensitive reproductive toxicity index. These results illustrated that both maternal impacts and offspring quality need to be considered for assessment of interaction of emerging contaminants.

Bioavailability of citalopram to Daphnia magna in the presence of suspended sediments with various properties.

The influence of suspended sediment (SPS) properties on the biological effects of antidepressant citalopram (CIT) was investigated in our study. For CIT exposure alone, the feeding behavior, energy available, glutathione-S-transferase (GST) activity of D. magna were vitally induced at 10 µg/L. In the presence of SPS, significant dose-dependent reduction in the ingestion and filtration rates were observed with the increase of SPS concentration, while SPS organic content (foc) of 1% exhibited the most serious aggravation. The protein was the main contributor to detoxification and cellular protection under the stress of CIT and SPS. Obvious disturbance effects on the malonaldehyde content, catalase and GST activities were observed for SPS of 0.1 g/L, 60-90 µm and foc of 2%. Overall, the important role of SPS properties on the biological effects of CIT should be taken into consideration for the accurate risk assessment of pollutants.

Precision Biotransformation of Emerging Pollutants by Human Cytochrome P450 Using Computational-Experimental Synergy: A Case Study of Tris(1,3-dichloro-2-propyl) Phosphate.

Precision biotransformation is an envisioned strategy offering detailed insights into biotransformation pathways in real environmental settings using experimentally guided high-accuracy quantum chemistry. Emerging pollutants, whose metabolites are easily overlooked but may cause idiosyncratic toxicity, are important targets of such a strategy. We demonstrate here that complex metabolic reactions of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) catalyzed by human CYP450 enzymes can be mapped via a three-step synergy strategy: (i) screening the possible metabolites via high-throughout (moderate-accuracy) computations; (ii) analyzing the proposed metabolites in vitro by human liver microsomes and recombinant human CYP450 enzymes; and (iii) rationalizing the experimental data via precise mechanisms using high-level targeted computations. Through the bilateral dialogues from qualitative to semi-quantitative to quantitative levels, we show how TDCIPP metabolism especially by CYP3A4 generates bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) as an O-dealkylation metabolite and bis(1,3-dichloro-2-propyl) 3-chloro-1-hydroxy-2-propyl phosphate (alcoholß-dehalogen) as a dehalogenation/reduction metabolite via the initial rate-determining H-abstraction from αC- and ßC-positions. The relative yield ratio [dehalogenation/reduction]/[O-dealkylation] is derived from the relative barriers of H-abstraction at the ßC- and αC-positions by CYP3A4, estimated as 0.002 to 0.23, viz., an in vitro measured ratio of 0.04. Importantly, alcoholß-dehalogen formation points to a new mechanism involving successive oxidation and reduction functions of CYP450, with its precursor aldehydeß-dehalogen being a key intermediate detected by trapping assays and rationalized by computations. We conclude that the proposed three-step synergy strategy may meet the increasing challenge of elucidating biotransformation mechanisms of substantial synthesized organic compounds in the future.

Influence of suspended sediment on the bioavailability of benzophenone-3: Focus on accumulation and multi-biological effects in Daphnia magna.

The UV-filter benzophenone-3 (BP3) tends to associate with suspended sediment (SPS) due to hydrophobicity, which could alter its toxicological effects on non-target aquatic organisms. In this study, the freshwater cladoceran Daphnia magna (D. magna) was selected as a model organism to investigate the impacts of the source and composition of SPS on the accumulation and multiple toxicological effects (from the molecular level to individual level) of BP3. Among the three components of SPS, amorphous organic carbon (AOC) and minerals promoted the body burden of BP3, while black carbon (BC) inhibited the bioaccumulation. The inhibition effects of BP3 on swimming and feeding behaviors of D. magna were also enhanced due to the presence of AOC and BC. Compared with BP3 exposure alone, higher oxidative stress and neurotoxicity were observed in the presence of SPS containing AOC, BC and minerals, corresponding to that superoxide dismutase, catalase and glutathione-S-transferase activities were further induced, and acetylcholinesterase activity was inhibited. Furthermore, BP3 induced mRNA expression levels of the endocrine system (ecdysone receptor, cytochrome P450 CYP314) and metabolic system (toxicant nuclear receptor HR96, P-glycoprotein), and the presence of SPS containing AOC, BC and minerals exhibited an enhanced effect. Combined with all endpoints, evident relationship was observed between the bioaccumulation level and the response of individual behavior and molecular biomarkers. The results demonstrated that the effects of SPS compositions on bioaccumulation and toxicological effects of organic UV-filters should be considered in aquatic environments.

Influence of dissolved organic matter on the accumulation, metabolite production and multi-biological effects of environmentally relevant fluoxetine in crucian carp (Carassius auratus).

Fluoxetine is a widely prescribed antidepressant that has been frequently detected in aquatic environments and is associated with a series of neurological, behavioural and neuroendocrine disruptions in nontarget organisms. However, studies on its effects in fish under realistic environmental conditions are still limited. In this study, we determined the influences of an environmentally relevant concentration of fluoxetine (100 ng/L) on crucian carp (Carassius auratus) in the presence of dissolved organic matter (DOM). Endpoints that were assessed included accumulation of fluoxetine and metabolite formation as well as related biological responses involving neurotransmission and metabolic processes. Fluoxetine was significantly bioconcentrated in the fish brain and liver and largely transformed to the active metabolite norfluoxetine. Brain neurotransmission processes related to serotonin and choline and liver metabolic status were simultaneously altered. DOM added at 1 mg/L had no effect on the accumulation of fluoxetine or its metabolites in different tissues of the fish. However, at 10 mg/L DOM facilitated fluoxetine and norfluoxetine accumulation in the liver, brain, kidney, gill and bile tissues of the fish. The neuroendocrine-disrupting effects on fish caused by fluoxetine were also enhanced by the co-addition of DOM at 10 mg/L. Binding with fluoxetine and the inhibition of metabolic functions caused by DOM may be responsible for this increase in effects. These findings imply that at high concentrations DOM can increase the toxicity of environmentally relevant concentrations of fluoxetine to fish.

Ecological impact assessment of 110 micropollutants in the Yarlung Tsangpo River on the Tibetan Plateau.

In this study, the occurrences of 110 micropollutants in the surface waters and sediments collected at eight sampling sites along the middle reaches of the Yarlung Tsangpo River were investigated in winter. A total of 47 and 45 micropollutants were detected in at least one water or sediment sample, respectively, and their total concentrations reached 790.2 ng/L and 186.5 ng/g on a dry weight basis, respectively. Their composition profiles demonstrated that the majority of micropollutants were polycyclic aromatic hydrocarbons (PAHs) and UV filters. The mixture risk quotient (MRQ) values of the detected micropollutants regularly exceeded 1 for aquatic organisms at all sampling sites, and fish and invertebrates are the more sensitive organisms. The diversity and evenness of the zooplankton levels had a clear negative correlation with the micropollutant occurrences in water. The top 10 mixture components belonging to the UV filter and PAH categories explained more than 80% and 95% of the mixture risk for chronic and acute toxicology, respectively. This study is the first investigation of the presence and risk assessment of 110 micropollutants in the Yarlung Tsangpo River Basin and offers new insights into the ecological security of the water resources of the Tibetan Plateau.

Residues, bioaccumulation, and trophic transfer of pharmaceuticals and personal care products in highly urbanized rivers affected by water diversion.

Little information is available on the bioaccumulation and trophic transfer of pharmaceuticals and personal care products (PPCPs) in urban rivers system, particularly for those affected by water transfer. Herein, a comprehensive study was conducted to investigate the biological residues, bioaccumulation and trophic transfer of 45 PPCPs in the Nanjing Qinhuai River system under the background of water diversion projects. A total of 30 compounds were detected with a descending order of overall concentration as plankton > benthic mollusc > fish (except grass carp). Higher biological residues were observed in the downstream than those in the upstream, with the largest increase for fish (136.4 %) and the lowest increase for phytoplankton (5.4 %). However, the bioaccumulation classifications of most PPCPs were unchanged among the three different water-diversion regions. Trophic magnification factors (TMFs) of organic UV filters (homosalate, oxybenzone, ethylhexyl methoxycinnamate and octocrylene) ranged from 1.23 to 2.04, suggesting trophic magnification potential, while trophic dilution for pharmaceuticals (sertraline, citalopram, caffeine and roxithromycin) with TMFs of 0.42 to 0.50 were observed. A notable positive correlation was observed between the pH-dependent distribution coefficient (logDow) and the TMFs of the PPCPs (P < 0.05). Although the human health hazard assessment indicated no immediate health risk via the consumption of freshwater food, attention should be paid to the joint effects of PPCPs.

Distribution, sources and human risk of perfluoroalkyl acids (PFAAs) in a receiving riverine environment of the Nanjing urban area, East China.

In recent years, perfluoroalkyl acids (PFAAs) have become ubiquitously distributed in water environments, especially in riverine waters receiving effluents from wastewater treatment plants (WWTPs) in urban areas. With rapid economic development, China has become the main market of manufacturing and consuming fluorinated products. While studies concerning PFAAs on dimension of urban water system are scarce. To elucidate the distribution patterns of PFAAs using multi-matrices, the effects of spatial-temporal factors on the partition behaviors of PFAAs were investigated in different riverine environments in the downtown area of Nanjing, East China. Predominated by perfluorooctanoic acid (PFOA), sum PFAAs (∑PFAAs) in the water phase were with concentrations of 0.8˜274.6 ng/L, characteristically higher in the dry season and lower in the wet season. The composition profiles in sediments (∑PFAAs 0.8˜11.4 ng/g dry weight) differed from that in water, being with a larger proportion of longer-chain PFAAs. The main sources of PFAAs in water were identified as industrial discharge, uncontrolled sewage discharge or WWTP effluents, surface runoff and nonpoint sources. The discharge fluxes of ∑PFAAs from Nanjing City can reach at 916.5 g/d for the Qinhuai River and 134.1 g/d for WWTPs along the Yangtze River. Fish have been shown to accumulate PFAAs in various tissues, with bioaccumulation positively correlated with perfluoroalkyl chain length. The hazard indexes associated with consumption of river fish were estimated low for Nanjing local population.

Multilevel ecotoxicity assessment of environmentally relevant bisphenol F concentrations in Daphnia magna.

With the pressure to ban or limit the use of Bisphenol A (BPA), substitutes such as bisphenol F (BPF) are applied to various commodities and generally detected in aquatic systems worldwide. To understand the potential ecological risk of BPF, the acute toxicity as well as behavioural, physiological and biochemical parameters of the water flea Daphnia magna were assessed. Following BPF exposure at concentrations ranging from 0.1 µg L-1 to 100 µg L-1, phenotypic traits including growth development, fecundity and swimming activity were significantly inhibited in response to exposure to sublethal concentrations (1-100 µg L-1) of BPF, which had a positive relationship with the activity of antioxidant enzymes. Moreover, the acetylcholinesterase (AChE) activity, which was strictly associated with the behavioural changes, was clearly inhibited, which was also obviously related to the heart rate and thoracic limb activity. Compared to the toxicity of BPA, BPF induces similar toxic effects, and the health concerns regarding the use of these alternatives should be highlighted.

Occurrence, spatial-temporal distribution and ecological risks of pharmaceuticals and personal care products response to water diversion across the rivers in Nanjing, China.

Water diversion projects have been continuously used to alleviate water quality issues that arise during urbanization. However, studies about whether it has possible effects on the status of pharmaceutical and personal care products (PPCPs) are limited. In this study, the occurrence trends and spatial-temporal distribution characteristics of 50 PPCPs were investigated in surface water, suspended particulate matter (SPM) and sediments in Nanjing urban rivers under the background of the water diversion project from the Yangtze River to the Qinhuai River. In the four field campaigns that were embarked on April to July 2018, a total of 40, 38 and 24 PPCPs were detected in surface water, SPM and sediments, respectively, with overall concentrations of 138-1990 ng/L, 3214-33,701 ng/g and 12.1-109 ng/g dry weight (dw) among nine sampling sites. The excessive concentration of caffeine (20.6-905 ng/L) may be evidence of the direct discharge of untreated sewage and an obvious indicator of the overall concentrations of PPCPs. The PPCPs contamination levels in surface water were increased along with the direction of the water diversion in urban runoff, and decreased by 8-31% due to the increase in volume attributable to the water diversion. The distribution coefficients (Kd) of pollutants in the SPM-water phases (3.0-5.6 L/kg) were two orders of magnitude higher than those in the sediment-water phases (0.3-3.3 L/kg). And the positive correlations between their log Kow and SPM-water log Kd values indicated SPM was the important carrier determining the fate of organic UV filters. Furthermore, the results of ecological risk assessment demonstrated that although the increase in the volume of water caused by the water diversion reduced the overall ecological risks of PPCPs in urban rivers, the current contamination level still represents high risks to algae and fish.

Bioconcentration, behavioral, and biochemical effects of the non-steroidal anti-inflammatory drug diclofenac in Daphnia magna.

The non-steroidal anti-inflammatory drug (NSAID) diclofenac is one of the most frequently studied as well as controversially discussed pharmaceutically active drug on the subject of its relevance to the environment. This study was conducted to assess the bioconcentration potential of diclofenac and its behavioral and biochemical effects in Daphnia magna. The bioconcentration factors of diclofenac determined after 48 h of aqueous exposure in Daphnia magna were 70.94 and 8.02 for the nominal exposure concentrations of 5 and 100 µg/L, respectively. Diclofenac exposure obviously decreased the filtration and ingestion rates of the daphnids. A significant increase of the acetylcholinesterase activity that was observed in this study indicates that diclofenac might not have neurobehavioral toxicity in Daphnia magna. Significant induction of malondialdehyde content is an indication of overproduction of reactive oxygen species leading to oxidative damage in daphnids after diclofenac exposure. Moreover, significant inhibition of the superoxide dismutase, catalase, and glutathione reductase activities implies that the antioxidant defense system of Daphnia magna was overwhelmed. Also, significant inhibition of glutathione s-transferase activity might point to the fact that the enzyme was not capable to detoxify diclofenac in Daphnia magna. These findings indicate that diclofenac can accumulate and consequently stimulate behavioral and biochemical disturbances in Daphnia magna.

Bioconcentration of the antiepileptic drug carbamazepine and its physiological and biochemical effects on Daphnia magna.

Owing to its persistence, carbamazepine an antiepileptic drug is regularly detected in the aquatic environment. The motive for our research was to assess the bioconcentration, physiological and biochemical effects of carbamazepine in Daphnia magna. A 48 h aqueous exposure of carbamazepine yielded bioconcentration factors of 202.56 and 19.95 in Daphnia magna for the respective nominal treatments of 5 and 100 µg/L. Apparently, the inhibition of the capability of Daphnia magna to obtain food attributable to carbamazepine exposure will reduce their fitness to reproduce as well as to grow. Also, a significant alteration in the phototactic behaviour of Daphnia magna exposed to carbamazepine is maladaptive since it will increase their chance of being preyed upon in the surface water during daylight. Again, a significant decline in the acetylcholinesterase activity observed herein brings to light the neurotoxicity of carbamazepine to Daphnia magna. Moreover, significant inhibition of the superoxide dismutase, catalase and glutathione reductase activities coupled with the simultaneous induction of the malondialdehyde content imply that carbamazepine evoked a life-threatening oxidative stress that overpowered the antioxidant defence system of Daphnia magna. These observations confirm that carbamazepine can accumulate and consequently cause negative physiological and biochemical changes to wild Daphnia magna populations.

Accumulation, metabolite and active defence system responses of fluoxetine in zebrafish embryos: Influence of multiwalled carbon nanotubes with different functional groups.

Studies on the bioavailability of organic contaminants adsorbed to nanomaterials are increasing. In this study, we investigated the interaction between fluoxetine (FLX) and three multiwalled carbon nanotubes (MWCNTs) with different functional groups in zebrafish (Danio rerio) embryos, focusing on the FLX accumulation, the formation of the metabolite norfluoxetine (NFLX), and the active defence system responses. The accumulation of FLX in zebrafish was intensified by MWCNTs (46-99%), which simultaneously facilitated the formation of the metabolite NFLX by 23-167%. The consistent enhancement revealed that the absorbed FLX is bioavailable in zebrafish. Moreover, the coexisting MWCNTs further promoted the influences of FLX on the active defence system in zebrafish (e.g. antioxidant and metabolic function), eliciting the defence function. The influences of MWCNTs on the bioavailability of FLX in zebrafish could be ordered as OH-MWCNTs > COOH-MWCNTs > pristine MWCNTs. The release of FLX from MWCNTs in biofluids may partially contribute to these significant alterations. In particular, MWCNTs themselves may also modulate the bioavailability of FLX in zebrafish by downregulating the gene expression of membrane ATP-binding cassette transporter (abcb4). These findings demonstrated that MWCNTs increased the bioavailability of FLX in zebrafish, especially the functionalized MWCNTs. The production of metabolites may be a useful bio-endpoint to evaluate the bioavailability of adsorbed contaminants on nanomaterials.