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Halogenated compounds are particularly important in pharmaceutical and agrochemical products. Biochemical halogenation with halogenases are environmental friendly reactions with high efficiency. Recently, the two new chlorinases (ClA1 and ClA2) were discovered from soil bacteria. However, the protein structure of ClA2 was not identified. Here, we determined the high-resolution crystal structure of ClA2. This structure will help us to understand the catalytic mechanism of chlorinase, and explain the catalytic process of the coupled chlorinase-fluorinase system, which offers the prospect of arising rapid radiolabeling protocols under mild conditions. • Resolves the crystal structure of the CIA2. • Discloses unique catalytic center of CIA2, which different from the CIA1 and SalL. • The Arg243 in CIA2 may lead to the higher trans -catalysis efficiency. [ABSTRACT FROM AUTHOR]

2,2,4,4-tetra-brominated diphenyl ether (PBDE-47)—the dominant homologue of polybrominated diphenyl ethers—is a toxic environmental pollutant in the aquatic environment that continuously exists and bioaccumulates in the aquatic food chain. In experimental disease models, melatonin (MEL) has been reported to attenuate necroptosis and inflammatory responses. To further explore the mechanism underlying PBDE-47 toxicity and the mitigative impact of MEL detoxification, in this study, fish kidney cell models of PBDE-47 poisoning and/or MEL treatment were developed. The Ctenopharyngodon idellus kidney (CIK) cell line was treated with PBDE-47 (100 μM) and/or MEL (60 μM) for 24 h. Experimental data suggest that PBDE-47 exposure resulted in the enhancement of cytoplasmic Ca2+ concentration, induction of calcium dysmetabolism, decrease in the miR-140-5p miRNA level, upregulation of Toll-like Receptor 4 (TLR4) and nuclear factor-kappaB (NF-κB), triggering of receptor interacting serine/threonine kinase-induced necroptosis, and NF-κB pathway mediated secretion of inflammatory factors in CIK cells. PBDE-47-induced CIK cell damage could be mitigated by MEL through the regulation of calcium channels and the restoration of disorders of the miR-140-5p/TLR4/NF-κB axis. Overall, MEL relieved PBDE-47-induced necroptosis and the secretion of inflammatory factors through the miR-140-5p/TLR4/NF-κB axis. These findings enrich the current understanding of the toxicological molecular mechanisms of the PBDE-47 as well as the detoxification mechanisms of the MEL. [Display omitted] • Melatonin alleviates PBDE-47-induced calcium dysmetabolism in CIK cells. • Melatonin mitigates CIK cell damage by restoring miR-140-5p/TLR4/NF-κB. • Melatonin relieves PBDE-47-induced necroptosis and inflammatory factor secretion. [ABSTRACT FROM AUTHOR]

As a kind of environmental pollutant, heavy metal Cadmium (Cd) exists widely in the environment. It is well known that Cd can accumulate and cause damage in liver, kidney and other organs. However, there are few studies on the immune cytotoxicity of Cd to fish. In particular, there are few studies on the toxicity of Cd to the head kidney lymphocytes of common carp. In order to further explore these mechanisms, we established an Cd exposure model in vitro. At the same time, we used the natural antioxidant astilbin (AST) to treat the cells to study its antagonistic effect on the toxicity of Cd. After exposure to Cd, the level of oxidative stress in head kidney lymphocytes increased, and the mRNA and protein expression of apoptosis-related markers Fas, FADD, Caspase8 and Caspase3 increased significantly (P < 0.05), which led to lymphocytes apoptosis. Hoechst staining and AO/EB staining also showed that the level of apoptosis increased after exposure to Cd. This is consistent with our previous research results. AST treatment reduced oxidative stress and apoptosis induced by Cd. In addition, oxidative stress inhibitor NAC could also reduce head kidney lymphocytes apoptosis induced by Cd, indicating that oxidative stress was involved in this process. Our results suggested that AST can alleviate the apoptosis of carp head kidney lymphocytes induced by Cd through oxidative stress. This study enriches the theoretical mechanism of Cd toxicity to fish head kidney lymphocytes, and puts forward a method to solve the toxicity of Cd, which provides a theoretical and research basis for the in vivo study of animal models in the future. [Display omitted] • Cadmium induced apoptosis and oxidative stress of carp lymphocytes. • Astilbin could reduce apoptosis of lymphocytes induced by cadmium. • Oxidative stress was involved in apoptosis of lymphocytes induced by cadmium. [ABSTRACT FROM AUTHOR]

Chlorocholine chloride (CCC) is a plant growth regulator used worldwide that is detectable in cereals, fruits and animal products. The health effects of CCC exposure have raised public concern. Our previous research showed that CCC exposure decreased testosterone synthesis in pubertal rats. However, little is known about whether and how pubertal CCC exposure impacts spermatogenesis. In this study, we used BALB/c mice and spermatogonia-derived GC-1 cells to examine CCC-induced spermatogenic dysfunction. In vivo , pubertal CCC exposure led to decreased testicular weight, decreased testicular germ cells and poor sperm quality. This effect worsened after cessation of CCC exposure for the next 30 days. RNA-seq and western blot analysis revealed that CCC induced aryl hydrocarbon receptor (AhR) signaling, endoplasmic reticulum stress (ERS) and ferritinophagy. Increased iron content and lipid peroxidation levels were also observed in CCC-treated testes. In vitro , it was identified that iron overload mediated by enhanced ferritinophagy occurred in CCC-treated GC-1 cells, which might be attributed to the PERK pathway in ERS. Further, for the first time, our study elucidated the involvement of AhR in CCC-induced iron overload, which aggravated testicular oxidative damage via lipid peroxidation. Considering the adverse impact of CCC exposure on rodents, supportive evidence from GC-1 cells, and the critical importance of spermatogenesis on male development, the effects of CCC on the male reproduction warrant increased attention. [Display omitted] • CCC pubertal exposure led to spermatogenesis disorders which remained after cessation of CCC exposure for the next 30 days. • CCC-induced iron overload by ferritinophagy activation contributed to lipid peroxidation in GC-1 cells. • PERK pathway in endoplasmic reticulum stress triggered ferritinophagy activation in CCC-treated cells. • AhR was involved in CCC-induced ROS production and PERK-dependent iron overload, which caused testicular oxidative damage. [ABSTRACT FROM AUTHOR]

Triptolide (TP) is the major bioactive component of traditional Chinese medicine Tripterygium wilfordii Hook. F., a traditional Chinese medicinal plant categorized within the Tripterygium genus of the Celastraceae family. It is recognized for its therapeutic potential in addressing a multitude of diseases. Nonetheless, TP is known to exhibit multi-organ toxicity, notably hepatotoxicity, which poses a significant concern for the well-being of patients undergoing treatment. The precise mechanisms responsible for TP-induced hepatotoxicity remain unresolved. In our previous investigation, it was determined that TP induces heightened hepatic responsiveness to exogenous lipopolysaccharide (LPS). Additionally, natural killer (NK) cells were identified as a crucial effector responsible for mediating hepatocellular damage in this context. However, associated activating receptors and the underlying mechanisms governing NK cell represented innate lymphoid cell (ILC) activation remained subjects of inquiry and were not yet investigated. Herein, activating receptor Killer cell lectin like receptor K1 (NKG2D) of group 1 ILCs was specifically upregulated in TP- and LPS-induced acute liver failure (ALF), and in vivo blockade of NKG2D significantly reduced group 1 ILC mediated cytotoxicity and mitigated TP- and LPS-induced ALF. NKG2D ligand UL16-binding protein-like transcript 1 (MULT-1) was found upregulated in liver resident macrophages (LRMs) after TP administration, and LRMs did exhibit NK cell activating effect. Furthermore, M1 polarization of LRMs cells was observed, along with an elevation in intracellular tumor necrosis factor (TNF)-α levels. In vivo neutralization of TNF-α significantly alleviated TP- and LPS-induced ALF. In conclusion, the collaborative role of group 1 ILCs and LRMs in mediating hepatotoxicity was confirmed in TP- and LPS-induced ALF. TP-induced MULT-1 expression in LRMs was the crucial mechanism in the activation of group 1 ILCs via MULT-1-NKG2D signal upon LPS stimulation, emphasizing the importance of infection control after TP administration. [Display omitted] • NKG2D is the crucial activating receptor of group 1 ILC in TP- and LPS-induced ALF. • Recognition of NKG2D and LRM MULT-1 promotes group 1 ILC activation. • M1 polarized LRMs mediate hepatocellular damage by TNF-α in TP- and LPS-induced ALF. • Collaborating of Group 1 ILCs and LRMs lead to occurrence of ALF induced by TP and LPS. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is an environmental pollutant produced by industrial activities, which has no known physiological benefits to organisms. In our previous study, the transcriptomic profiles of carp head kidney exposed to Cd was analyzed by genomics technique, and confirmed that miRNAs are important in the head kidney injury of carp induced by Cd, but the specific biological mechanism was unclear. In order to further explore the effect of Cd on carp head kidney lymphocyte damage, we established a model of Cd exposure in vitro. The results showed that Cd could increase the expression of Bax (Bcl‐2 associated X protein), Caspase9 (Cysteinyl aspartate specific proteinase 9) and Caspase3 (Cysteinyl aspartate specific proteinase 3), inhibit the expression of Bcl-2 (B cell lymphoma/leukemia 2), and induce apoptosis of carp head kidney lymphocytes. In our previous study, we screened the differentially expressed miRNA in Cd-treated lymphocytes by high-throughput sequencing, and found that there was a significant difference in the expression of miR-9-5p. The expression trend of miR-9-5p in the vitro model was the same as that of high-throughput sequencing. We screened the differentially expressed gene FKBP5 (FK506-binding protein 51) in lymphocytes treated with Cd. It was confirmed by double luciferase reporter gene analysis that FKBP5 was the target gene of miR-9-5p. We established the overexpression/knockdown model of miR-9-5p in carp head kidney lymphocyte in vitro. The results showed that miR-9-5p could inhibit the expression of FKBP5, increase the phosphorylation level of Akt, inhibit apoptosis and improve the cell survival rate in carp head kidney lymphocytes. Together, Cd could down-regulate the expression of miR-9-5p, target up-regulate the expression of FKBP5, inhibit the phosphorylation of Akt, and promote the apoptosis of carp head kidney lymphocytes through mitochondrial pathway. [Display omitted] • First time to verify the targeting relationship between miR-9-5p and FKBP5 in fish. • Cd can inhibit the p -Akt and induce apoptosis of carp head kidney lymphocytes. • miR-9-5p can inhibit Cd-induced apoptosis of carp head kidney lymphocytes. [ABSTRACT FROM AUTHOR]

Evaluating the cost-effectiveness of emission trading system (ETS) will explore how to control the total emission amount while minimizing the economic cost. Most related studies employ the difference-in-differences (DID) and multi-period DID models. However, this research highlights the superiority of construction technique and estimation results in the synthetic DID model, and applies it to a new scenario for evaluating the cost-effectiveness of China's pilot ETS. From the construction technique, the synthetic DID model synthesizes more desirable control groups and allows more flexibility in matching treatment units with extreme values by setting weight combinations and intercept terms. From the estimation results, the treatment effects are considered more reliable because ideally satisfy the parallel trend assumption. Specifically, the synthetic DID model indicated that the pilot ETS effectively reduced the marginal abatement cost (MAC) by 24.39%, whereas the traditional DID and multi-period DID models may have overestimated the policy effects by 98.48% and 71.09%. The main reason was the MAC has shown a downward trend before the policy implementation. Moreover, the estimation results of heterogeneity analysis and mechanism test in different models were also different. The synthetic DID model integrates the strengths of the DID model and synthetic control method (SCM), making a methodologically grounded contribution to the existing policy evaluation system. • The frontier synthetic DID model is applied in a new scenario. • Reveal the technical superiority and accurate results of the synthetic DID model. • The traditional DID and multi-period DID models may overestimate the policy effects. • The synthetic DID model integrates the strengths of the DID model and SCM method. [ABSTRACT FROM AUTHOR]

There is evidence suggesting the participation of non-coding RNAs in male reproductive dysfunction induced by lead, and the significance of microRNAs has been highlighted recently because of their essential roles in gene regulatory networks. To comprehensively understand the functions of miRNA and the regulatory networks, RNA sequencing was carried out to obtain miRNA expression profiles in mice testes exposed to low dose Pb for 90 days at the onset of puberty. In total, 44 differentially expressed miRNAs with 26 up-regulated and 18 down-regulated were identified between 200 mg/L Pb group and control group (p < 0.05). Enrichment analysis confirmed that the target genes of DE miRNAs might participate in the metabolism of testicular cells. Furthermore, a miRNA-mRNA co-expression network consisting of 19 miRNAs and 106 mRNAs and a competing endogenous RNA network of lncRNA-miRNA-mRNA including 179 genes were established. Finally, the expressions of 4 miRNAs (mmu-miR-451a, mmu-miR-133a-3p, mmu-miR-1a-3p and mmu-miR-486a-3p) and 4 mRNAs (Gramd1b, Tcf7l2, Mov10 and Srcin1) involved in regulatory networks were verified by RT-qPCR. In conclusion, our research might provide targets for the mechanism studies of miRNAs in reproductive toxicity of Pb. • MiRNA expression profiles are changed in testes after low dose lead exposure. • MiRNAs and their target genes might participate in the metabolism of testicular cells. • Mmu-miR-486a-3p might play an important role in testicular injury induced by low dose lead exposure. [ABSTRACT FROM AUTHOR]

The insecticide chlorpyrifos plays an important role in agricultural production and is widely used because of its excellent insecticidal ability. However, the mechanism by which chlorpyrifos causes lymphocyte death remains unclear. In this study, transcriptomic techniques were used to analyze the head kidney tissues of carp (Cyprinus carpio) treated with chlorpyrifos. Subsequently, we screened out differentially expressed genes (DEGs) and performed the corresponding processing in the head kidney lymphocyte. Then, the intracellular calcium content and necrosis were detected by fluorescence staining, real-time fluorescence quantitative PCR, and flow cytometry. Our results showed that the expression of T cell receptor gamma (TCR γ) was significantly decreased, and TCR γ was inhibited after chlorpyrifos treatment. Also, TCR γ significantly increased the abundance of calcium channel messenger RNA (mRNA). To verify this result, we established the TCR γ overexpression group and found that the reverse results were observed in TCR γ of in the overexpression group. The results of cytoplasmic calcium concentration detection, calcium staining, and flow cytometry confirmed the conclusion of increased calcium in the cytoplasm. The function of TCR γ significantly enhanced the mRNA expression levels of necrosis-related genes, and this conclusion was evidenced by the result of necrotic flow detection. Our results showed that chlorpyrifos could inhibit TCR γ in carp lymphocytes and induce calcium-dependent necrosis. [Display omitted] • TCR γ knockdown and overexpression models were established in lymphocytes. • TCR γ involved in the process of chlorpyrifos-dependent necrosis in common carp lymphocytes. • TCR γ involved in calcium overload in common carp lymphocytes. [ABSTRACT FROM AUTHOR]

Polybrominated diphenyl ethers (PBDEs) exist in aquatic environments with nephrotoxicity to non-target aquatic species. Melatonin (MT) exhibits an inhibitory effect of oxidative stress and apoptosis in various diseases. 2, 2′, 4, 4′-tetrabromodiphenyl ether (BDE-47) is the main homolog of PBDE samples. Therefore, we investigated the toxic mechanism of BDE-47 and the alleviation effect of MT, the ctenopharyngodon idellus kidney (CIK) cells were treated with BDE-47 (100 μM) and/or MT (60 μM) for 24 h. Firstly, BDE-47 exposure could inhibit oxidative stress-related antioxidant enzymes (T-AOC, SOD, CAT and GPx) and increase the content of malondialdehyde (MDA) to cause oxidative stress. Secondly, BDE-47 enhanced mitochondrial division and inhibited fusion to induce mitochondrial membrane potential in CIK cells. BDE-47 enhanced the mRNA and protein levels of mitochondrial-pathway apoptosis related genes (Cas 3, Cyt-c, and BAX). Thirdly, BDE-47 treatment decreased the expression levels of mitochondrial-related regulatory factors AMPK-Sirt1-PGC-1α signal pathway. Intriguingly, BDE-47-induced oxidative stress, mitochondrial pathway apoptosis and mitochondrial dynamics disorder could be alleviated by MT treatment. Overall, we concluded that MT could relieve BDE-47-induced oxidative stress, mitochondrial dysfunction and apoptosis through the AMPK-Sirt1-PGC-1α axis. These results enrich the mechanisms of BDE-47 poisoning and reveal that MT treatment may be a potential strategy for solving BDE-47 poisoning. [Display omitted] • Melatonin (MT) relieves oxidative stress induced by BDE-47 in CIK cells. • MT mitigates the mitochondrial dysfunction via the AMPK-Sirt1-PGC-1α axis under BDE-47. • Melatonin (MT) relieves apoptosis caused by BDE-47 exposure in CIK cells. [ABSTRACT FROM AUTHOR]

This study investigated the presence of 18 dioxin-like and non-dioxin-like polychlorinated biphenyls (dl- and ndl-PCBs), heavy metals (Cd, Hg, Pb, and As) in Chinese mitten crabs (Eriocheir sinensis) and their distribution in Jiangsu, China. Risk assessment and source apportionment were employed for evaluating the eco-toxicological impact and human exposure. It was found that the compositions of PCBs varied spatially, suggesting different sources of pollutants, whilst PCB 28, 105, 114, and 126 were consistently found in all sample types, suggesting a common pollution source remained, and the bio-accumulation process was in effect. The total PCBs in sediment were found much higher than in water, and brown meat had the highest and most diverse PCB congeners among all tissues. The presence of heavy metals was found in all samples in descending order of As>Cd>Pb>Hg and in the order of shell>brown meat>white meat>gill for crabs. The results of risk assessment indicated that the potential carcinogenic and non-carcinogenic risks were within the acceptable range for long-term consumption of the crabs overall. However, the highest toxic equivalent (TEQ), carcinogenic, and non-carcinogenic risks were all recorded in Location C, where dl-PCB 126, 169, and As contributed to the majority of the risks. The ecological risk posed by all HMs was low, but cases of serious point source pollution have been found in the investigated regions, and risks caused by Cd individually should raise concerns. Source apportionment study revealed that the contaminants mostly originated from anthropogenic activities. Natural deposition and transportation played an important role as well. [Display omitted] • Human activities and natural processes responsible for PCBs and heavy metals in Chinese mitten crabs in Jiangsu, China. • Brown crab meat had the highest amount and diversity of PCB congeners among all crab tissues. • Dioxin-like PCB 126, 169, and arsenic account for most of health risks. Cadmium contributes to moderate ecological risk. • Health risks are within the acceptable range, but near unacceptable thresholds at the current crab ingestion rate. [ABSTRACT FROM AUTHOR]

The stochastic and intermittent features of wind power as well as the high percentage of wind power grid-connected significantly increase the additional operating costs of the power system. It is difficult to accurately calculate the impact of complex fluctuations in wind power on additional operating costs. To solve the above problems, a power system operating cost model adapted to various wind power fluctuation processes is established. Firstly, based on a two-layer clustering strategy, different types of wind power fluctuations are obtained. Then, a production simulation model of the power system with renewable energy is established. The production simulation model costs include thermal plant operating costs, energy storage system operating costs, positive reserve costs and negative reserve costs. With the optimization objective of minimizing the total operating cost of the power system, realistic and representative system operating parameters and cost samples are obtained for various wind power fluctuations and different wind power grid-connected scenarios. Finally, a data-driven approach based on a deep neural network algorithm is proposed to achieve precise mapping between wind energy fluctuations and the operating costs of power systems and thermal power units, and the operating costs of the power system during the four seasons with different types of wind power fluctuations can be precisely analyzed. The results demonstrate that the method proposed in this paper has high simulation accuracy for the overall simulation operating cost of the power system and the operating cost of thermal power plants. The simulation errors are 4%–18% and 3%–13%, respectively, which verified the effectiveness of the method. • Two-layer clustering strategy with variable time windows identifies wind power fluctuation types. • A simulation model of power system operating costs is established based on a data-driven approach. • Power system operating costs simulation accuracy varies with seasons and wind power fluctuations types. [ABSTRACT FROM AUTHOR]

Collagen is an active macromolecule, but direct comparisons between different sources were scarce. The purpose of this study was to compare collagen from three fish species to find a collagen with higher bioactivity. Collagen from the swim bladder of Ctenopharyngodon idella , Nibea coibor and Protonibea diacanthus were isolated and named CASC, NASC and PASC, respectively. SDS-PAGE and spectroscopic analysis indicated that ASCs contained triple-helix type I collagen. The microstructure of collagen after lyophilization was uniform and porous. In addition, DSC analysis of the ASCs showed that the denaturation temperature (T d) and melting temperature (T m) were 79 °C–93 °C and ∼216 °C, respectively. Moreover, the antioxidant activity of ASCs and its effect on fibroblast viability and collagen synthesis were investigated. Current studies have shown that ASCs had antioxidant capacity and were not toxic to fibroblasts. NASC had a higher antioxidant capacity (Hydroxyl, DPPH and ABTS radical scavenging rates were 33.73%, 33.49% and 89.81%, respectively) and significantly promoted fibroblast viability compared to the other two ASCs. It was further found that NASC can promote collagen synthesis in fibroblasts. Collagen extracted from swim bladder may be a promising functional product for the food, cosmetics and biomedical fields. • ASCs from three swim bladders shared typical physicochemical properties of collagen. • ASC from the Nibea coibor swim bladder had better biological activity. • Swim bladder collagen is a promising functional product for different fields. [ABSTRACT FROM AUTHOR]

• Theory-guided HCP is proposed to introduce domain knowledge and prior information as hard constraints into neural networks through projection. • A projection matrix is constructed based on the governing equation, which can be regarded as a non-trainable activation function in the neural networks. • Experiment shows that hard constraint can effectively reduce data demand and increase prediction accuracy with sparse and partial observations. Machine learning models have been successfully used in many scientific and engineering fields. However, it remains difficult for a model to simultaneously utilize domain knowledge and experimental observation data. The application of knowledge-based symbolic artificial intelligence (AI) represented by expert systems is limited by the expressive ability of the model, and data-driven connectionism AI represented by neural networks is prone to produce predictions that might violate physical principles. In order to fully integrate domain knowledge with observations and make full use of the strong fitting ability of neural networks, this study proposes theory-guided hard constraint projection (HCP). This deep learning model converts physical constraints, such as governing equations, into a form that is easy to handle through discretization, and then implements hard constraint optimization through projection in a patch. Based on rigorous mathematical proofs, theory-guided HCP can ensure that model predictions strictly conform to physical mechanisms in the constraint patch. The training process of theory-guided HCP only needs a small amount of labeled data (sparse observation), and it can supervise the model by combining the coordinates (label-free data) with domain knowledge. The performance of the theory-guided HCP is verified by experiments based on a published heterogeneous subsurface flow problem. The experiments show that theory-guided HCP requires fewer data, and achieves higher prediction accuracy and stronger robustness to noisy observations, than the fully connected neural networks and soft constraint models. Furthermore, due to the application of domain knowledge, theory-guided HCP possesses the ability to extrapolate and can accurately predict points outside of the range of the training dataset. [ABSTRACT FROM AUTHOR]