Comprehensive evaluation of chiral penflufen metabolite (penflufen-3-hydroxy-butyl): Identification, synthesis, enantioseparation, toxicity and enantioselective metabolism.

Identification and evaluations of pesticide metabolites are necessary for risk assessment and toxicological research. In this study, the metabolites of penflufen (a widely used chiral pesticide) in rat liver microsomes were identified using liquid chromatography Q-Exactive Plus mass spectrometry. In total, 17 penflufen metabolites were identified, and most of them were hydroxylation products, which were generated by oxygenation at different candidate sites of penflufen. The relative abundance of metabolite M12 (penflufen-3-hydroxy-butyl, 32 %) was the largest, followed by M8 (15.6 %) and M2 (12.8 %). The major metabolite penflufen-3-hydroxy-butyl was first synthesized by 11 reactions with a 99.73 % purity. The absolute configuration of M12 enantiomers were confirmed after preparing enantiomers, and establishing the enantioseparation method. The M12 enantiomers toxicity to Danio rerio (LC50, >10 mg/L) and four kinds of phytopathogens (EC50, 148-34969 mg/L) were significantly lower than parents (LC50, 0.449-24.3 mg/L; EC50, 0.027-92.0 mg/L). In rat liver microsomes, approximately 40-47 % of the penflufen enantiomers were metabolized to M12 enantiomers, and R-penflufen was preferentially metabolized. The generation concentrations of S-M12 were higher than R-M12 after 10 min, and the metabolic half-lives of R-M12 (29.0-32.5 min) were shorter than S-M12 (35.2-38.1 min), and were approximately 4 times longer than parent penflufen enantiomers (4.5-9.5 min). Simultaneously, the generated contents (relative contents) of M8 (27.1-57 %) and M10 (2.22-8.36 %) from S-penflufen were lower than those from R-penflufen (M8, 24.7-92.4 %; M10, 27.4-69.5 %). The enantioselective evaluations of M12, M10 and M8 deserve further study. These findings were helpful in understanding the fate and risks of chiral penflufen.

Congenital microtia patients: the genetically engineered exosomes released from porous gelatin methacryloyl hydrogel for downstream small RNA profiling, functional modulation of microtia chondrocytes and tissue-engineered ear cartilage regeneration.

BACKGROUND: Mesenchymal stem cells (MSCs) exosomes were previously shown to be effective in articular cartilage repairing. However, whether MSCs exosomes promote mature cartilage formation of microtia chondrocytes and the underlying mechanism of action remains unknown. Additionally, some hurdles, such as the low yield and unsatisfactory therapeutic effects of natural exosomes have emerged when considering the translation of exosomes-therapeutics to clinical practices or industrial production. Herein, we investigated the roles of human adipose-derived stem cells (ADSCs) exosomes in modulating microtia chondrocytes and the underlying mechanism of action. Special attention was also paid to the mass production and functional modification of ADSCs exosomes. RESULTS: We firstly used porous gelatin methacryloyl (Porous Gelma) hydrogel with pores size of 100 to 200 µm for 3D culture of passage 2, 4 and 6 ADSCs (P2, P4 and P6 ADSCs, respectively), and obtained their corresponding exosomes (Exo 2, Exo 4 and Exo 6, respectively). In vitro results showed Exo 2 outperformed both Exo 4 and Exo 6 in enhancing cell proliferation and attenuating apoptosis. However, both Exo 4 and Exo 6 promoted chondrogenesis more than Exo 2 did. Small RNA sequencing results indicated Exo 4 was similar to Exo 6 in small RNA profiles and consistently upregulated PI3K/AKT/mTOR signaling pathway. Notably, we found hsa-miR-23a-3p was highly expressed in Exo 4 and Exo 6 compared to Exo 2, and they modulated microtia chondrocytes by transferring hsa-miR-23a-3p to suppress PTEN expression, and consequently to activate PI3K/AKT/mTOR signaling pathway. Then, we designed genetically engineered exosomes by directly transfecting agomir-23a-3p into parent P4 ADSCs and isolated hsa-miR-23a-3p-rich exosomes for optimizing favorable effects on cell viability and new cartilage formation. Subsequently, we applied the engineered exosomes to in vitro and in vivo tissue-engineered cartilage culture and consistently found that the engineered exosomes could enhance cell proliferation, attenuate apoptosis and promote cartilage regeneration. CONCLUSIONS: Taken together, the porous Gelma hydrogel could be applied to exosomes mass production, and functional modification could be achieved by selecting P4 ADSCs as parent cells and genetically modifying ADSCs. Our engineered exosomes are a promising candidate for tissue-engineered ear cartilage regeneration.

Efficacy and safety of verapamil vs triamcinolone acetonide for keloids and hypertrophic scars: A systematic review and meta-analysis.

The treatment of keloids and hypertrophic scars remains a challenge. Although triamcinolone acetonide (TAC) is one of the most common and effective treatments for keloids and hypertrophic scars, TAC is not effective in some patients, and some may even experience adverse outcomes. Verapamil might be considered a safe alternative to TAC. The aim of this study was to compare the efficacy and safety of verapamil and TAC for the treatment of keloids and hypertrophic scars. Three databases (Medline, EMBASE, and CENTRAL database) were electronically searched from 1997 to December 2019. Article selection was limited to randomized controlled trials (RCTs) and controlled clinical trials (CCTs). Two authors independently assessed the selection of studies, risk of bias, and extracted the data. Mean differences (MDs) were computed for continuous variables, risk ratios (RRs) were computed for dichotomous variables, and 95% confidence intervals (CIs) were calculated for both assessments. Five RCTs were included, comprising a total of 215 patients (273 scars). Vancouver Scar Scale (VSS) parameters (such as height, vascularity, pliability, and pigmentation) were reported as the outcome measures and provided detailed values in four studies. No significant differences were observed between verapamil and TAC in the reduction of height (MD 0.57, 95% CI -0.94 to 2.08, P = .46), vascularity (MD 0.30, 95% CI -0.42 to 1.02, P = .41), pliability (MD 0.67, 95% CI -1.12 to 2.47, P = .46), and degree of pigmentation (MD 0.14, 95% CI -0.41 to 0.69, P = .61). Adverse outcomes were reported in four studies. The results showed that the incidence of telangiectasia and skin atrophy that used verapamil was significantly lower than that for TAC. Concerning the treatment of keloids and hypertrophic scars, even though verapamil was safer than TAC, TAC worked faster than verapamil. Furthermore, we did not find any clear evidence that verapamil was more or less effective than TAC. Considering the high degree of safety of verapamil, we suggest that verapamil might be used as an alternative treatment when TAC results in adverse outcomes.

Effect of Platelet-Rich Fibrin on Fat Grafting in Animal Models: A Meta-Analysis.

BACKGROUND: Autologous fat grafting has been widely used in plastic and reconstructive surgery, but one of the main reasons for limiting its application is the high resorption rate. Platelet-rich fibrin (PRF) is a new generation of platelet concentrate that has recently been used to improve the survival rate of fat grafts. The purpose of this study was to evaluate the effect of PRF on fat grafting. METHODS: Animal studies in four databases (PubMed, Cochrane library, Ovid, and Wan fang database) were searched up to July 2019. A meta-analysis was performed to compare PRF + fat grafting and fat grafting alone or platelet-rich plasma (PRP) + fat grafting in animal models. RESULT: Six studies with 83 animals (123 fat graftings) were included in our meta-analysis. The fat survival rate (mean difference (MD) 0.14, P < 0.00001) and the microvessel density (MVD) (standardized mean difference 4.20, P = 0.02) of the PRF + fat group were significantly higher than that of the fat alone group. There was no significant difference between the PRF + fat group and PRP + fat group in the fat survival rate (MD 0.05, P = 0.06). CONCLUSION: This study found that PRF combined with fat grafting may have an effect on improving the survival rate and MVD of fat grafts. However, when comparing the effects of PRF and PRP on the fat survival rate, there is currently no clear evidence to prove the difference between them. More preclinical and clinical studies are necessary to further clarify the effect of PRF on fat grafting in humans. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

A one-pot approach to pyridyl isothiocyanates from amines.

A one-pot preparation of pyridyl isothiocyanates (ITCs) from their corresponding amines has been developed. This method involves aqueous iron(III) chloride-mediated desulfurization of a dithiocarbamate salt that is generated in situ by treatment of an amine with carbon disulfide in the present of DABCO or sodium hydride. The choice of base is of decisive importance for the formation of the dithiocarbamate salts. This one-pot process works well for a wide range of pyridyl ITCs. Utilizing this protocol, some highly electron-deficient pyridyl and aryl ITCs are obtained in moderate to good yields.

Fluorescent probes for insect ryanodine receptors: candidate anthranilic diamides.

Diamide insecticides with high efficacy against pests and good environmental safety are broadly applied in crop protection. They act at a poorly-defined site in the very complex ryanodine (Ry) receptor (RyR) potentially accessible to a fluorescent probe. Two N-propynyl analogs of the major anthranilic diamide insecticides chlorantraniliprole (Chlo) and cyantraniliprole (Cyan) were accordingly synthesized and converted into two fluorescent ligands by click reaction coupling with 3-azido-7-hydroxy-2H-chromen-2-one. The new diamide analogs and fluorescent ligands were shown to be nearly as potent as Chlo and Cyan in inhibition of [3H]Chlo binding and stimulation of [3H]Ry binding in house fly thoracic muscle RyR. Although the newly synthesized compounds had only moderate activity in insect larvicidal activity assays, their high in vitro potency in a validated insect RyR binding assay encourages further development of fluorescent probes for insect RyRs.

Risk Perception, Perceived Government Coping Validity, and Individual Response in the Early Stage of the COVID-19 Pandemic in China.

As a major crisis event, the COVID-19 pandemic has affected the global economy, threatened the lives of the public, and caused varying degrees of impact on the public. Previous studies have shown that risk perception and government response had different impacts on the public, but they revealed more about the independent impact of risk perception and government response on the public. This study will comprehensively consider the impacts of these two factors on the behavior of the public in the early stage of the epidemic. We analyzed data from an online survey in the early days of the COVID-19 pandemic in China and categorized individual behaviors into three dimensions: entertainment and travel, work, and the stockpile of supplies. In addition, we defined the risk perception variables by two dimensions: knowledge of the epidemic itself and knowledge of the consequences of the epidemic. At the same time, we used an exploratory factor analysis to construct the variable of perceived government coping validity and then adopted the ordinal logit model for analysis. The results showed that in terms of entertainment and travel, people would not be affected even if they fully understood the epidemic itself; once they were aware of the negative social consequences of the epidemic, people would suspend entertainment and travel to prevent the spread of the virus. As for work or employment, people would not stop working or employment even if they realized the infectivity and harmfulness of the disease and its social consequences. Furthermore, fear of COVID-19 and the perception of uncontrolled COVID-19 significantly positively affected people's material stockpiling behavior. These results indicate that different risk perceptions had different effects on individual responses, and individual behaviors reflected different coping logics. In addition, the government's effective response to the epidemic would significantly reduce the negative impacts of the epidemic on the three dimensions of people's responses. These conclusions have certain policy implications for preventing and responding to outbreaks in other countries.

Transformation of a Dopamine D2 Receptor Agonist to Partial Agonists as Novel Antipsychotic Agents.

Designed ligands of G protein-coupled receptors can exert a spectrum of modulating effects, varying from full agonists and partial agonists to antagonists and inverse agonists. For the dopamine D2 receptor (D2R), partial agonist activity is the pharmacological feature of the third-generation antipsychotics, including aripiprazole, brexpiprazole, and cariprazine. Started from a benzofuran-derived D2R full agonist O4LE6 (4), which was identified using a structure-based method by us in previous studies, a series of D2R partial agonists were designed and synthesized by introducing different tail groups. Among them, compound 10b showed excellent activity in D2R pharmacological assays. Further optimizations using a structural rigidification approach led to the discovery of brain-penetrant compounds 29c and 29d, which exhibited potent antipsychotic effects in the mouse hyperlocomotion model. Compound 29c also showed excellent drug-like pharmacokinetic properties in rats and qualifies as an antipsychotic agent that is worth further evaluations.

Surgical management of auricular arteriovenous malformations: A literature review.

Auricular arteriovenous malformations (AVMs) can cause a variety of symptoms that seriously impact the patient's appearance, life, and mental well-being. Surgery is the primary management method for auricular AVMs, but there is no consensus on how to surgically manage auricular AVMs. In this article, we document a comprehensive review of the characteristics, classification, and surgical interventions to treat auricular AVMs.

Adipose stem cells-released extracellular vesicles as a next-generation cargo delivery vehicles: a survey of minimal information implementation, mass production and functional modification.

OBJECTIVES: To investigate current situation of minimal information implementation highlighted by minimal information for studies of extracellular vesicles 2018 (MISEV2018) guidelines, and explore technological advances towards mass production and functional modification in aesthetic, plastic and reconstructive surgery. METHODS: Original articles on extracellular vesicles (EVs) of adipose stem cells (ASCs) were identified. Statistics upon minimal information for EVs research, such as species, cell types, culture conditions, conditioned media harvesting parameters, EVs isolation/storage/identification/quantification, functional uptake and working concentration, were analyzed. RESULTS: The items of cell culture conditions such as passage number, seeding density, conditioned media harvesting time, functional uptake and working concentration were poorly documented, with a reporting percentage of 47.13%, 54.02%, 29.89%, 62.07% and 36.21%, respectively. However, there were some studies not reporting information of ASCs origin, culture medium, serum, EVs isolation methods, quantification and identification of EVs, accounting for 3.45%, 10.34%, 6.90%, 3.45%, 18.39% and 4.02%, respectively. Serum deprivation and trophic factors stimuli were attempted for EVs mass production. Several technological advances towards functional modification included hypoxia pre-condition, engineering EVs and controlled release. Presently, ASCs EVs have been applied in multiple fields, including diabetic/non-diabetic wound healing, angiogenesis, inflammation modulation, fat grafting, hair regeneration, antiaging, and healing and regeneration of cartilage/bone/peripheral nerve/tendon. CONCLUSION: Our results highlight normative reporting of ASCs EVs in functional studies to increase reliability and reproducibility of scientific publications. The advances towards mass production and functional modification of ASCs EVs are also recommended to enhance therapeutic effects.

Dual-acting antitumor agents targeting the A2A adenosine receptor and histone deacetylases: Design and synthesis of 4-(furan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine derivatives.

Based on its inhibition by antagonists, the A2A adenosine receptor (A2AAR) has attracted attention as an anti-tumor drug target; however, in preclinical models and clinical trials, A2AAR antagonists have so far shown only limited efficacy as standalone therapies. The design of dual-acting compounds, targeting the A2AAR and histone deacetylases (HDACs), is used here as an approach to the discovery of novel and more potent antitumor agents. Based on the core structures of the A2AAR antagonists V-2006 and CPI-444, novel 4-(furan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine derivatives were designed as such dual-acting compounds. The binding affinities for A2AAR of all the new compounds were tested, and their HDAC inhibitory activity was evaluated. Compounds with balanced A2AAR antagonism and HDAC inhibition were tested for their in vitro anti-proliferative activity and pharmacokinetic properties. One of the compounds, 14c (4-(2-(6-Amino-4-(furan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-N-(2-amino-phenyl)benzamide) showed an overall favorable pharmacokinetic profile; in the mouse MC38 xenograft model, it showed potent anti-tumor effects with inhibition rates of 44% (90 mg/kg, po, bid) and 85% (60 mg/kg, ip, bid), respectively.

Design, synthesis and mode of action of novel 3-chloro-6-pyrazolyl picolinate derivatives as herbicide candidates.

BACKGROUND: Picolinate/picolinic acid compounds are an important class of synthetic auxin herbicides. To explore the herbicidal activity of 6-pyrazolyl picolinate compounds, a series of 3-chloro-6-pyrazolyl-picolinate derivatives was designed and synthesized. RESULTS: Twenty-five 3-chloro-6-pyrazolyl-picolinate derivatives synthesized were tested for herbicidal activity and the IC50 value of compound c5 to the growth of Arabidopsis thaliana root was 27 times lower than that of the commercial herbicide clopyralid. Compound c5 displayed better post-emergence herbicidal activity and broader (Picloram, Clopyralid, Aminopyralid) herbicidal spectrum at a dosage of 400 g ha-1 in comparison with clopyralid; it also was safe to wheat and maize at this dosage. Arabidopsis thaliana phenotypes and expression of auxin-response genes demonstrated that compound c5 might be a novel auxin-type herbicide. Molecular docking analyses revealed that compound c5 had stronger binding ability to receptor AFB5 (auxin signaling F-box protein 5) than clopyralid. CONCLUSION: These 6-pyrazolyl picolinate compounds could be used as potential lead structures for the discovery of a novel synthetic auxin herbicide. © 2021 Society of Chemical Industry.

2-Phenylcyclopropylmethylamine Derivatives as Dopamine D2 Receptor Partial Agonists: Design, Synthesis, and Biological Evaluation.

Partial agonist activity at the dopamine D2 receptor (D2R) is the primary pharmacological feature of the third-generation antipsychotics─aripiprazole, brexpiprazole, and cariprazine. However, all these drugs share a common phenyl-piperazine moiety as the primary pharmacophore. In this study, we designed and synthesized a series of novel compounds based on the 2-phenylcyclopropylmethylamine (PCPMA) scaffold and studied their pharmacological activity at the D2R. A number of potent D2R partial agonists were identified through binding affinity screening and functional activity profiling in both G protein and ß-arrestin assays. The structure-functional activity relationship results showed that the spacer group is crucial for fine-tuning the intrinsic activity of these compounds. Compounds (+)-14j and (+)-14l showed good pharmacokinetic properties and an unexpected selectivity against the serotonin 2A (5-HT2A) receptor. Preliminary suppressive effects in a mouse hyperlocomotion model proved that these PCPMA-derived D2R partial agonists are effective as potential novel antipsychotics.

Structure-Based Design of Dual-Acting Compounds Targeting Adenosine A2A Receptor and Histone Deacetylase as Novel Tumor Immunotherapeutic Agents.

Adenosine is an immunosuppressive factor in the tumor microenvironment mainly through activation of the A2A adenosine receptor (A2AR), which is a mechanism hijacked by tumors to escape immune surveillance. Small-molecule A2AR antagonists are being evaluated in clinical trials as immunotherapeutic agents, but their efficacy is limited as standalone therapies. To enhance the antitumor effects of A2AR antagonists, dual-acting compounds incorporating A2AR antagonism and histone deacetylase (HDAC) inhibitory actions were designed and synthesized, based on co-crystal structures of A2AR. Compound 24e (IHCH-3064) exhibited potent binding to A2AR (Ki = 2.2 nM) and selective inhibition of HDAC1 (IC50 = 80.2 nM), with good antiproliferative activity against tumor cell lines in vitro. Intraperitoneal administration of 24e (60 mg/kg, bid) inhibited mouse MC38 tumor growth with a tumor growth inhibition rate of 95.3%. These results showed that dual-acting compounds targeting A2AR and HDAC are potentially immunotherapeutic agents that are worth further exploring.

Value of Partial Sensory Rhizotomy in the Microsurgical Treatment of Trigeminal Neuralgia Through Retrosigmoid Approach.

PURPOSE: Microvascular decompression (MVD) is the most effective surgical procedure for the treatment of refractory primary trigeminal neuralgia (TN), but due to the presence of non-neurovascular compression (NVC), the application of MVD is limited. In some cases, partial sensory rhizotomy (PSR) is required. The purpose of this study was to compare the outcome of MVD and MVD+PSR in the treatment of primary TN and to evaluate the application value of PSR in the treatment of TN. PATIENTS AND METHODS: We retrospectively analyzed the postoperative outcomes of patients who received MVD or MVD+PSR for the first time from the same surgeon in the neurosurgery department of China-Japan Friendship Hospital from March 2009 to December 2017. A total of 105 patients were included in the data analysis, including 40 in the MVD group and 65 in the MVD+PSR group. RESULTS: The MVD group had an effectiveness rate of 60% and a recurrence rate of 31.4% after an average follow-up of 49.4 months. The MVD+PSR group had an average effectiveness rate of 69.2% and a recurrence rate of 28.6% after an average follow-up of 71.4 months. There was no statistically significant intergroup difference in long-term effectiveness (p=0.333) or recurrence rates (p=0.819). The incidence of facial numbness was significantly higher in the MVD+PSR group than in the MVD group (83.1% vs 7.5%; p<0.001). However, facial numbness had no significant effect on the patients' daily life. CONCLUSION: MVD+PSR and MVD have the same effectiveness in the treatment of primary TN. MVD+PSR is associated with a higher incidence of facial numbness than MVD, but the difference does not affect the patients' daily life. PSR should have a place in the treatment of TN by posterior fossa microsurgery.

The Long-Term Outcomes and Predictors of Microvascular Decompression with or without Partial Sensory Rhizotomy for Trigeminal Neuralgia.

PURPOSE: Microvascular decompression (MVD) and MVD combined with partial sensory rhizotomy (PSR) are effective surgical treatments for idiopathic trigeminal neuralgia (TN). The aim of this study was to compare the long-term outcomes of both MVD and MVD+PSR for the treatment of TN and to identify the factors that may influence the long-term outcomes after MVD or MVD+PSR. PATIENTS AND METHODS: From March 2009 to December 2017, 99 patients with idiopathic TN who underwent MVD or MVD+PSR in our hospital (40 MVD, 59 MVD+PSR) were included in the study. The indications for MVD+PSR were as follows: vessels only contacted the nerve root, absence of arterial conflict, or failing to completely decompress from the arteries or veins. All patients were treated by one neurosurgeon and were followed up for at least 1 year. The outcomes were assessed with the Barrow Neurological Institute (BNI) Pain Intensity Scale. RESULTS: The average follow-up duration was 63.0 months (range, 13.2-118.8 months). Patients in the MVD group were younger than those in the MVD+PSR group (55.1 years and 60.5 years, respectively, P=0.012). A total of 62.5% of the patients in the MVD group and 69.5% of the patients in the MVD+PSR group had favorable long-term outcomes. The Kaplan-Meier survival analysis showed no significant difference in long-term outcomes between the two groups (P=0.202). No factors were associated with long-term outcomes after MVD. For MVD+PSR, a long duration of the disease (odds ratio (OR) 6.967, P=0.016) was associated with unfavorable long-term outcomes, whereas pure arterial compression (OR 0.131, P=0.013) was associated with favorable long-term outcomes. CONCLUSION: For patients who are not suitable to undergo pure MVD, MVD+PSR can be used as an effective alternative. For MVD+PSR, patients with a long duration of symptoms may have poor long-term outcomes, while patients with pure arterial compression may have favorable long-term outcomes.

Factors That May Affect Delayed Relief Of Trigeminal Neuralgia After Microneurosurgery And The Long-Term Outcomes Associated With Delayed Relief.

OBJECTIVE: Microvascular decompression (MVD) combined with partial sensory rhizotomy (PSR) with the retrosigmoid approach has become the most effective surgical treatment for trigeminal neuralgia (TN). There is variability in the pain relief processes observed in postoperative patients. The purpose of this study was to investigate delayed relief (DR) and its predictors after MVD and/or PSR for the treatment of TN and study the long-term effects associated with DR. METHODS: Patients with primary TN who underwent MVD and/or PSR by the same surgeon at the China-Japan Friendship Hospital from March 2009 to December 2017 were included in the study, and all patients were followed for at least 1 year after the operation. DR was defined as follows: no changes in the Barrow Neurological Institute (BNI) score on the third day after surgery and a BNI score of I-II in the absence of any medication after a period of pain. Preoperative, intraoperative and postoperative differences were compared between the DR and non-DR groups, and the relationships between the various factors and DR was analyzed. RESULTS: A total of 105 patients, including 20 patients with DR (19%), 78 patients with non-DR (74%), and 7 patients without relief, were included in this study. The follow-up period ranged from 13 months to 118 months (average, 5.39 years/65 months). The duration of postoperative pain in the DR group was 3-365 days, with an average of 108 days. Statistical analysis found that no factor predicted the occurrence of DR, and the occurrence of postoperative DR did not affect the long-term effects observed in patients. CONCLUSION: DR did not affect the long-term effects after MVD and/or PSR. Therefore, it is recommended that patients should be monitored for approximately 3 months after MVD and/or PSR and then evaluated for surgical effects. No reoperations should be performed immediately.

Selective bioaccumulation, biomagnification, and dissipation of hexachlorocyclohexane isomers in a freshwater food chain.

Hexachlorocyclohexane isomers (HCHs) are persistent organic pollutants (POPs), having potential risks to humans and ecosystem. This work evaluated the propensity of organisms to accumulate, eliminate, and transfer HCHs along the food chain (Tubifex tubifex and common carp (Cyprinus carpio)). The accumulation of HCHs from water by worms and carp was observed, and the concentrations increased with exposure time. After 8 days, the HCH concentrations in organisms remained stable. The accumulation factor (AF) values of HCHs in T. tubifex were higher than those in carp, indicating that the bioaccumulation abilities of HCHs in T. tubifex were higher than those in carp. The contaminated worms as a dietary source in the food chain led to significantly higher bioaccumulation in carp. The biomagnification factor (BMF) values of HCH isomers were all greater than 1. In the dissipation experiments, the elimination was fast and the half-lives were shorter than 2.5 days. The enantioselective accumulation and dissipation of α-HCH enantiomers were observed in worms and carp (food chain), and the enantiomeric differences should be taken into consideration in the study of contaminants risk assessment. The results on trophic transfer of HCHs in a freshwater food chain should be helpful for better understanding the fate, transport, and transfer of HCHs in freshwater environments.

Assessment of tissue-specific accumulation, elimination and toxic effects of dichlorodiphenyltrichloroethanes (DDTs) in carp through aquatic food web.

Microcosms containing DDT spiked-sediment, Tubifex tubifex and carp (Cyprinus carpio) were constructed to simulate a freshwater system. The accumulation, elimination and toxic effects of DDT (p,p'-DDT, o,p'-DDT), and its metabolites DDD (p,p'-DDD, o,p'-DDD) and DDE (p,p'-DDE, o,p'-DDE) were studied in T. tubifex and carp. Tissue/organ distributions of DDTs were also investigated in carp. The bioaccumulation and elimination of DDT differed in T. tubifex, carp and its tissues/organs. Unimodal or bimodal distributions were observed, and the concentrations of DDT metabolites (DDD and p,p'-DDE) increased over time. The carp organ with the highest concentrations of DDTs (DDT, DDD and DDE) was the gill. The largest mass distribution of DDTs was also in gill, followed by muscle and gastrointestinal tract. Maximum levels of DDTs in whole carp and carp muscle were 161 and 87 ng/g, respectively; therefore, the levels of DDTs observed in carp in this study were insufficient to constitute a health concern if present in fish for human consumption. Significant changes were observed in some biomarkers, including superoxide dismutase, catalase, glutathione-S-transferase, glutathione, and carboxylesterase, in T. tubifex and carp tissues during DDT exposure. Tissue-specific accumulation of DDTs in carp can be a key indicator of exposure to environmentally relevant concentrations.