Comparison of cardiotoxicity induced by alectinib, apatinib, lenvatinib and anlotinib in zebrafish embryos.

Four tyrosine kinase inhibitors, alectinib, apatinib, lenvatinib and anlotinib, have been shown to be effective in the treatment of clinical tumors, but their cardiac risks have also raised concerns. In this study, zebrafish embryos at 6 h post fertilization (hpf) were exposed to the four drugs at concentrations of 0.05-0.2 mg/L until 72 hpf, and then the development of these embryos was quantified, including heart rate, body length, yolk sac area, pericardial area, distance between venous sinus and balloon arteriosus (SV-BA), separation of cardiac myocytes and endocardium, gene expression, vascular development and oxidative stress. At the same exposure concentrations, alectinib and apatinib had little effect on the cardiac development of zebrafish embryos, while lenvatinib and anlotinib could induce significant cardiotoxicity and developmental toxicity, including shortened of body length, delayed absorption of yolk sac, pericardial edema, prolonged SV-BA distance, separation of cardiomyocytes and endocardial cells, and downregulation of key genes for heart development. Heart rate decreased in all four drug treatment groups. In terms of vascular development, alectinib and apatinib did not inhibit the growth of embryonic intersegmental vessels (ISVs) and retinal vessels, while lenvatinib and anlotinib caused serious vascular toxicity, and the inhibition of anlotinib in vascular development was more obvious. Besides, the level of reactive oxygen species (ROS) in the lenvatinib and anlotinib treatment groups was significantly increased. Our results provide reference for comparing the cardiotoxicity of the four drugs.

Dimethyl fumarate induces cardiac developmental toxicity in zebrafish via down-regulation of oxidative stress.

Dimethyl fumarate (DMF) is an immunosuppressant commonly used to treat multiple sclerosis and other autoimmune diseases. Despite known side effects such as lymphopenia, the effect of DMF on cardiac development remains unclear. To assess this, we used zebrafish to evaluate the cardiac developmental toxicity of DMF. Our study showed that DMF reduced the survival rate of zebrafish embryos, with those exposed to 1, 1.3, and 1.6 mg/L exhibiting heart rate reduction, shortened body length, delayed yolk sac absorption, pericardial edema, increased distance from sinus venous to bulbus arteriosus, and separation of cardiomyocytes and endocardial cells at 72 hpf. Heart development-related genes showed disorder, apoptosis-related genes were up-regulated, and the oxidative stress response was down-regulated. Treatment with cysteamine ameliorated the heart development defects. Our study demonstrates that DMF induces cardiac developmental toxicity in zebrafish, possibly by down-regulating oxidative stress responses. This study provides a certain research basis for further study of DMF-induced cardiac developmental toxicity, and provides some experimental evidence for future clinical application and study of DMF.

Iron blocks autophagic flux and induces autophagosomes accumulation in microglia.

Iron is an essential dietary micronutrient for maintaining physiological homeostasis. However, disruption of cerebral iron regulation with the accumulation of iron in different brain structures appears to have a role in the pathogenesis of various neurodegenerative disorders. Studies have reported that autophagy induction could potentially mitigate progression in neurodegenerative diseases with iron deposition, but the relationship between autophagy and iron remains poorly understood. Meanwhile, abnormal autophagy in microglia is closely related to the occurrence of neurodegenerative diseases. Therefore, the effect of iron on microglia autophagy needs to be elaborated. In the present study, we found that iron induces autophagosome accumulation but inhibits its initiation in an Akt-mTOR pathway independent manner. Meanwhile, it caused autophagy flux defects and dysfunction of lysosomes. We also found that iron overload reduced the expression of Rab7, which is an essential protein for the fusion of autophagosomes and lysosomes. These results suggest that iron induces the accumulation of autophagosome in microglia and disrupts the autophagic flux in late stage of autophagy. Therefore, our work provides new insights into the molecular mechanisms of iron neurotoxicity.

Apatinib induces zebrafish hepatotoxicity by inhibiting Wnt signaling and accumulation of oxidative stress.

Apatinib, a small-molecule VEGFR2-tyrosine kinase inhibitor, has shown potent anticancer activity in various clinical cancer treatments, but also different adverse reactions. Therefore, it is necessary to study its potential toxicity and working mechanism. We used zebrafish to investigate the effects of apatinib on the development of embryos. Zebrafish exposed to 2.5, 5, and 10 µM apatinib showed adverse effects such as decreased liver area, pericardial oedema, slow yolk absorption, bladder atrophy, and body length shortening. At the same time, it leads to abnormal liver tissue structure, liver function and related gene expression. Furthermore, after exposure to apatinib, oxidative stress levels were significantly elevated but liver developmental toxicity was effectively ameliorated with oxidative stress inhibitor treatment. Apatinib induces down-regulation of key target genes of Wnt signaling pathway in zebrafish, and it is found that Wnt activator can significantly rescue liver developmental defects. These results suggest that apatinib may induce zebrafish hepatotoxicity by inhibiting the Wnt signaling pathway and up-regulating oxidative stress, helping to strengthen our understanding of rational clinical application of apatinib.

Sphk1 deficiency induces apoptosis and developmental defects and premature death in zebrafish.

The sphk1 gene plays a crucial role in cell growth and signal transduction. However, the developmental functions of the sphk1 gene during early vertebrate zebrafish embryo remain not completely understood. In this study, we constructed zebrafish sphk1 mutants through CRISPR/Cas9 to investigate its role in zebrafish embryonic development. Knockout of the sphk1 gene was found to cause abnormal development in zebrafish embryos, such as darkening and atrophy of the head, trunk deformities, pericardial edema, retarded yolk sac development, reduced heart rate, and premature death. The acetylcholinesterase activity was significantly increased after the knockout of sphk1, and some of the neurodevelopmental genes and neurotransmission system-related genes were expressed abnormally. The deletion of sphk1 led to abnormal expression of immune genes, as well as a significant decrease in the number of hematopoietic stem cells and neutrophils. The mRNA levels of cardiac development-related genes were significantly decreased. In addition, cell apoptosis increases in the sphk1 mutants, and the proliferation of head cells decreases. Therefore, our study has shown that the sphk1 is a key gene for zebrafish embryonic survival and regulation of organ development. It deepened our understanding of its physiological function. Our study lays the foundation for investigating the mechanism of the sphk1 gene in early zebrafish embryonic development.

Effects of Hermetia illucens larvae meal on the Pacific white shrimp (Litopenaeus vannamei) revealed by innate immunity and 16S rRNA gene sequencing analysis.

The larvae of the black soldier fly, Hermetia illucens, are now attracting attention and becoming promising sources for aquafeed ingredient due to the nutritious substance. However, the introduction of a novel ingredient into the recipe may have unpredictable effects on the innate immune function and gut bacteria composition of crustaceans. Therefore, the present study aimed to evaluate how dietary black soldier fly larvae meal (BSFLM) affected the antioxidant ability, innate immunity and gut microbiome of shrimp (Litopenaeus vannamei) fed with a practical diet, including the gene expression of Toll and immunodeficiency (IMD) pathways. Six experimental diets were formulated by replacing gradient levels of fish meal (0 %, 10 %, 20 %, 30 %, 40 % and 50 %) based on a commercial shrimp diet. Four replicates of shrimp were fed different diets three times daily for 60 days. Growth performance linearly decreased with increasing BSFLM inclusion. Results of antioxidative enzyme activities and gene expression suggested that low dietary BSFLM levels activated the antioxidant capacity of shrimp, while dietary BSFLM levels up to 100 g/kg may induce oxidative stress and inhibit glutathione peroxidase activity. Although traf6, toll1, dorsal and relish were significantly upregulated in different BSFLM groups, the expression of tak1 was significantly downregulated in groups containing BSFLM, implying the immune susceptibility may be weakened. Gut flora analysis indicated dietary BSFLM altered both beneficial and opportunistic pathogenic bacterial abundance, with low levels of dietary BSFLM increased the abundance of bacteria that may contribute to carbohydrate utilization, while high levels of dietary BSFLM may cause intestinal disease and low intestinal immune response. To conclude, 60-80 g/kg of dietary BSFLM showed no adverse effects on the growth, antioxidant capacity and gut flora of shrimp, which was the adequate level in shrimp diet. While 100 g/kg dietary BSFLM may induce oxidative stress and potentially weaken the innate immunity of shrimp.

Roxadustat induces hepatotoxicity in zebrafish embryos via inhibiting Notch signaling.

Roxadustat is a novel and effective small-molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PHI). However, little research has been done on its toxicity to vertebrate embryonic development. In this study, we used zebrafish to assess the effects of roxadustat on early embryonic development. Exposure to 14, 28, and 56 µM roxadustat resulted in abnormal embryonic development in zebrafish embryos, such as shortened body length and early liver developmental deficiency. Roxadustat exposure resulted in liver metabolic imbalance and abnormal liver tissue structure in adult zebrafish. In addition, roxadustat could up-regulate oxidative stress, and astaxanthin (AS) could partially rescue liver developmental defects by down-regulation of oxidative stress. After exposure to roxadustat, the Notch signaling is down-regulated, and the use of an activator of Notch signaling can partially rescue hepatotoxicity. Therefore, our research indicates that roxadustat may induce zebrafish hepatotoxicity by down-regulating Notch signaling. This study provides a reference for the clinical use of roxadustat.

Cyclosporine A induces hepatotoxicity in zebrafish larvae via upregulating oxidative stress.

As a powerful immunosuppressant, cyclosporine A (CsA) is widely used clinically. However, it has been found to have many side effects including nephrotoxicity and neurotoxicity. Despite this, some patients cannot avoid using CsA during pregnancy and this can be detrimental to both the patient and the foetus. This study used zebrafish as a model animal to evaluate the hepatotoxic effects of CsA in zebrafish embryos. Zebrafish embryos cultured at 72 post-fertilization (hpf) were exposed to three concentrations of CsA at 2.5 mg/L, 5 mg/L, and 10 mg/L for 72 h. Liver developmental defects, smaller or missing swim bladder, slower heart rate, reduced body length, and delayed yolk sac absorption were observed. The level of oxidative stress (ROS) increased with the increase of CsA concentration. The indicators of related oxidative stress kinase activities including malondialdehyde (MDA), catalase (CAT) and SOD, all appeared to significantly increased. The use of astaxanthin (ATX) to inhibit oxidative stress was found to be useful for rescuing zebrafish hepatic development defects. Therefore, our results suggest that CsA induces zebrafish embryonic hepatic development defects by activating the oxidative stress. The study of CsA-induced hepatic development defects of zebrafish embryos is helpful for clinical evaluation of the safety of CsA and enables the search for new use without side effects.

Presence of cerebral microbleeds is associated with cognitive decline in acromegaly.

Background: Cognitive decline in acromegaly has gained increasing attention. Cerebral microbleeds (CMBs) as radiographic markers for microvascular injury have been linked to various types of cognitive decline. However, the association between CMB formation and acromegaly has not yet been quantified. This study is designed to investigate the prevalence and the radiographic patterns of CMBs and the association between cognitive function and acromegaly-related CMBs in growth hormone (GH)-secreting pituitary adenoma, which is characterized by acromegaly. Methods: In a cohort of 55 patients with GH-secreting pituitary adenoma (acromegaly) and 70 healthy control (HC) patients, we determined the presence of CMBs using a 3.0-T MRI scanner. The numbers, locations, and grades of CMBs were determined via susceptibility-weighted imaging (SWI) and the Microbleed Anatomical Rating Scale. Obstructive sleep apnea (OSA) was assessed using the criteria of the American Academy of Sleep Medicine (AASM) Scoring Manual Version 2.2. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance within 3 days of admission. The association between CMBs and cognitive function as well as clinical characteristics was explored. Results: The incidence of CMBs was 29.1%, whereas that of OSA was 65.5% in acromegaly. There was a statistically significant difference in the prevalence of CMBs between subjects with and without acromegaly (29.1% and 5.3%, respectively) (p < 0.01). The age of acromegaly patients with CMBs was much younger compared with HCs with CMBs. Compared with HCs, a significant cognitive decline and the occurrence of OSA were demonstrated in patients with acromegaly (p < 0.01). Binary logistic regression analysis adjusted for age, education, and body mass index (BMI) revealed that CMB was an independent risk factor for cognitive impairment in patients with acromegaly (OR = 3.19, 95% CI 1.51-6.76, p = 0.002). Furthermore, in the logistic regression models adjusted for age, BMI, diabetes, and hypertension, OSA was independently associated with the occurrence of CMBs in patients with acromegaly (OR = 13.34, 95% CI 3.09-57.51, p = 0.001). Conclusions: A significant increase of CMBs was demonstrated in patients with acromegaly, which may be a result of OSA in acromegaly. The present study indicated that increasing CMBs are responsible for cognitive decline in patients with acromegaly.

Propranolol hydrochloride induces neurodevelopmental toxicity and locomotor disorders in zebrafish larvae.

Propranolol hydrochloride is the first-line drug for the clinical treatment of hypertension, arrhythmia, and other diseases. However, with the increasing use of this drug, its safety and environmental health have received more and more attention. In this study, aquatic vertebrate zebrafish were used as a model to study the toxic effects and mechanisms of propranolol hydrochloride. It was revealed that zebrafish larvae exposed to propranolol hydrochloride showed aberrant head nerve development and locomotor disorders. Additionally, exposure to propranolol hydrochloride could induce oxidative stress, alter the activities of AChE and ATPase, and disrupt the expression of genes involved in neurodevelopment and neurotransmitter pathways. More interestingly, the expression of Parkinson's disease-related genes was altered in zebrafish treated with propranolol hydrochloride. We detected the expression of genes related to the Wnt signaling pathway and found that their expression appeared to be down-regulated. The phenotype of nerve developmental defects and locomotor disorders can be effectively rescued by astaxanthin and Wnt activators. Collectively, the results suggest that propranolol hydrochloride may induce neurotoxicity and abnormal movement behavior with PD-like symptoms in zebrafish larvae.

Exposure to pyrazosulfuron-ethyl induces immunotoxicity and behavioral abnormalities in zebrafish embryos.

Pyrazosulfuron-ethyl is one of the most widely used herbicides in agriculture and can be widely detected in aquatic ecosystems. However, its biosafety, including its potential toxic effects on aquatic organisms and its mechanism, is still poorly understood. As an ideal vertebrate model, zebrafish, the effect of pyrazosulfuron-ethyl on early embryonic development and immunotoxicity of zebrafish can be well evaluated. From 10 to 72 h post fertilization (hpf), zebrafish embryos were exposed to 1, 5, and 9 mg/L pyrazosulfuron-ethyl which led in a substantial reduction in survival, total length, and heart rate, as well as a range of behavioral impairments. In zebrafish larvae, the number of neutrophils and macrophages was considerably decreased and oxidative stress levels increased in a dose-dependent way after pyrazosulfuron-ethyl exposure. And the expression of immune-related genes, such as TLR-4, MyD88 and IL-1ß, were downregulated by pyrazosulfuron-ethyl exposure. Moreover, pyrazosulfuron-ethyl exposure also inhibited motor behavior. Notch signaling was upregulated after exposure to pyrazosulfuron-ethyl, while inhibition of Notch signaling pathway could rescue immunotoxicity. Therefore, our findings suggest that pyrazosulfuron-ethyl has the potential to induce immunotoxicity and neurobehavioral changes in zebrafish larvae.

Pamiparib Induces Neurodevelopmental Defects and Cerebral Haemorrhage in Zebrafish Embryos via Inhibiting Notch Signalling.

Pamiparib is a poly ADP-ribose polymerase (PARP) inhibitor used in clinical studies, which can penetrate the blood-brain barrier efficiently. At present, there are few studies on its effect on vertebrate neurodevelopment. In this study, we exposed zebrafish embryos to 1, 2 and 3 µM of Pamiparib from 6 to 72 h post-fertilisation (hpf). Results showed that pamiparib can specifically induce cerebral haemorrhage, brain atrophy and movement disorders in fish larvae. In addition, pamiparib exposure leads to downregulation of acetylcholinesterase (AChE) and adenosine triphosphate (ATPase) activities, and upregulation of oxidative stress which then leads to apoptosis and disrupts the gene expression involved in the neurodevelopment, neurotransmitter pathways and Parkinson's disease (PD) like symptoms. Meanwhile, astaxanthin can partially rescue neurodevelopmental defects by downregulating oxidative stress. After exposure to pamiparib, the Notch signalling is downregulated, and the use of an activator of Notch signalling can partially rescue neurodevelopmental toxicity. Therefore, our research indicates that pamiparib may induce zebrafish neurotoxicity by downregulating Notch signalling and provides a reference for the potential neurotoxicity of pamiparib during embryonic development.

The relationship between anal disease and quality of life: a bibliometric study.

Background: Anal disease has a significant impact on patients' quality of life (QoL), and surgical treatment may further diminish QoL. The purpose of this study was to conduct bibliometric analysis to investigate the profile of studies on anorectal disease-related QoL. Methods: The database of Science Citation Index Expanded (SCI-E) in Web of Science Core Collection (WOSCC) was searched. The search terms were "anal diseases" and "quality of life". The bibliometrix package of R software was used to analyze the literature on anorectal diseases and QoL. The content of the analysis included the following: the number of papers published in this field by each country, the cooperation relationship between countries, the number of papers published by institutions, the cooperation relationship between institutions, the number of papers published by researchers, the cooperation relationship between researchers, the citations of researchers, the number of articles published in journals, and the use of keywords. Results: A total of 1,130 related research literature records were retrieved in this study. An annually increasing trend was detected in the number of published papers and the number of citations. Developed countries in Europe and America, mainly the United States, the United Kingdom (UK), and Germany, were in a leading position in this field. The Cleveland Clinic Foundation and Mayo Clinic in the United States, St. Mark's Hospital in the UK, and the University of Toronto in Canada were the leading research institutions in this field. The top 3 researchers with the most published papers were Feza H. Remzi, Bo Shen, and Victor W. Fazio. Collaboration among researchers was clustered. There were more high-quality related articles in professional journals of anal diseases. The use of keywords suggested a temporal change in research focus, but randomized controlled studies were found to be lacking. Conclusions: Asian countries should participate in more collaborative research projects in the field of anorectal disease, and more randomized controlled studies should be conducted overall.

Lenvatinib induces cardiac developmental toxicity in zebrafish embryos through regulation of Notch mediated-oxidative stress generation.

Due to an increasing number of abused drugs dumped into the wastewater, more and more drugs are detected in the water environment, which may affect the survival of aquatic organisms. Lenvatinib is a multi-targeted tyrosine kinase inhibitor, and is clinically used to treat differentiated thyroid cancer, renal epithelial cell carcinoma and liver cancer. However, there are few reports on the effects of lenvatinib in embryos development. In this study, zebrafish embryos were used to evaluate the effect of lenvatinib on cardiovascular development. Well-developed zebrafish embryos were selected at 6 h post fertilization (hpf) and exposed to 0.05 mg/L, 0.1 mg/L and 0.2 mg/L lenvatinib up to 72 hpf. The processed embryos demonstrated cardiac edema, decreased heart rate, prolonged SV-BA distance, inhibited angiogenesis, and blocked blood circulation. Lenvatinib caused cardiac defects in the whole stage of cardiac development and increased the apoptosis of cardiomyocyte. Oxidative stress in the processed embryos was accumulated and inhibiting oxidative stress could rescue cardiac defects induced by lenvatinib. Additionally, we found that lenvatinib downregulated Notch signaling, and the activation of Notch signaling could rescue cardiac developmental defects and downregulate oxidative stress level induced by lenvatinib. Our results suggested that lenvatinib might induce cardiac developmental toxicity through inducing Notch mediated-oxidative stress generation, raising concerns about the harm of exposure to lenvatinib in aquatic organisms.

Cyclosporine A Induces Cardiac Developmental Toxicity in Zebrafish by Up-Regulation of Wnt Signaling and Oxidative Stress.

Due to the widely application of Cyclosporine A (CsA) as an immunosuppressant in clinic, it is necessary to study its potential toxicity. Therefore, we used zebrafish as a model animal to evaluate the toxicity of CsA on embryonic development. Exposure of zebrafish embryos to CsA at concentrations of 5 mg/L, 10 mg/L, and 15 mg/L from 12 hpf to 72 hpf resulted in abnormal embryonic development, including cardiac malformation, pericardial edema, decreased heart rate, decreased blood flow velocity, deposition at yolk sac, shortened body length, and increased distance between venous sinus and arterial bulb (SV-BA). The expression of genes related to cardiac development was disordered, and the apoptotic genes were up-regulated. Oxidative stress level was up-regulated and accumulated in pericardium in a dose-dependent manner. Astaxanthin (ATX) treatment could significantly alleviate zebrafish heart defects. CsA induced up-regulation of Wnt signaling in zebrafish, and IWR-1, an inhibitor of Wnt signaling pathway, could effectively rescue the heart defects induced by CsA. Together, our study indicated that CsA induced cardiac developmental toxicity in zebrafish larvae through up-regulating oxidative stress and Wnt signaling, contributing to a more comprehensive evaluation of the safety of the drug.

Lenvatinib exposure induces hepatotoxicity in zebrafish via inhibiting Wnt signaling.

Lenvatinib is a multi-kinase inhibitor for widely treating thyroid cancer. However, little studies have been done about it or its toxicity on embryonic development of vertebrate. In this study, we used zebrafish to assess the effect of lenvatinib on early embryonic development. Exposure of zebrafish embryos to 58, 117, 176 nM lenvatinib induced abnormal embryonic development, such as decreased heart rate, pericardial edema, delayed yolk absorption, and bladder atrophy. Lenvatinib exposure reduced liver area and down-regulated liver developmental related genes. The proliferation of hepatocytes and the expression of apoptosis-related genes were significantly reduced.by Lenvatinib. Furthermore, the imbalance of liver metabolism and abnormal liver tissue structure were observed in adult zebrafish after Lenvatinib exposure. Oxidative stress was up-regulated by lenvatinib and astaxanthin partially rescued hepatic developmental defects via downregulating oxidative stress. After lenvatinib exposure, Wnt signaling was down-regulated, and activation of Wnt signaling partially rescued hepatic developmental defects. Therefore, these results suggested that lenvatinib might induce zebrafish hepatotoxicity by down-regulating Wnt signaling related genes and inducing oxidative stress. This study provides a reference for the potential hepatotoxicity of lenvatinib during embryonic development and raises health concern about the potential harm of exposure to lenvatinib for foetuses.

Multifunctional Zn-Ln (Ln = Eu and Tb) heterometallic metal-organic frameworks with highly efficient I2 capture, dye adsorption, luminescence sensing and white-light emission.

A new family of isostructural 3d-4f heterometallic metal-organic frameworks (HMOFs), [Zn3EuxTb2-x(TZI)4(DMA)5(H2O)3]·4DMA [x = 0 (1), 0.3 (2), 0.6 (3), 0.9 (4), 1 (5), 1.2 (6), 1.5 (7), 1.8 (8), 2 (9)], has been synthesized using the 5-(4-(tetrazol-5-yl) phenyl)isophthalic acid (H3TZI) ligand, LnIII ions and ZnII ions under solvothermal conditions. All HMOFs exhibit a (3,3,4,5,5)-connected 63·63(42·62·82)(4·65·8)(4·66·83) topology, which features three different types of motifs: one is a mononuclear ZnII ion and the other two motifs are binuclear [Zn(COO)3Ln] clusters. The adsorption experiments indicate that Zn3Tb2 (1) could efficiently remove almost all I2 from cyclohexane solution after 12 h and also showed better adsorption towards neutral red (NR) dye (adsorption: only the Zn3Tb2 (1) was taken as one representative). Simultaneously, the luminescence sensing showed that Zn3Tb2 (1) and Zn3Eu2 (9) have excellent response and sensitivity towards pollutants such as Fe3+ ions and 2,4,6-trinitrophenol (TNP) with high selectivity and a fairly low limit of detection through luminescence quenching effect. Moreover, seven trimetallic-doped HMOFs 2-8 analogues of Zn3Ln2 (single) HMOFs were designed and prepared, showing different changes of luminescent color. More interestingly, Zn3Eu1.5Tb0.5 (7) with white-light emission was fabricated by doping relative concentrations of Eu3+ and Tb3+ ions. To the best of our knowledge, Zn3Eu1.5Tb0.5 (7) represents a novel kind of heterometallic Zn3Ln2 HMOFs with white-light emission. It could be deduced that the excellent characteristics, namely strong typical luminescence emission of ZnII and LnIII ions, microporous channels, active open metal sites (tetra-coordinated ZnII-metal sites), and uncoordinated carboxylate O atoms and uncoordinated tetrazolate N atoms, made the above HMOFs an ideal platform for adsorption, luminescence sensing, and white-light emission. More significantly, these HMOFs are the first reported Zn-Ln heterometallic materials with the H3TZI ligand.

Study on the Pretreatment Process and Removal Rules of Sulfur-Containing Compounds for Medium- and Low-Temperature Coal Tar.

The heteroatoms (sulfur and nitrogen) and metals (ferrum and calcium) in coal tar can easily cause the corrosion of hydrogenation equipment, catalyst poisoning, and environmental pollution. These should be removed before coal tar is hydrogenated. In this study, with the acid refining method, the effects of three polyether demulsifiers (i.e., PD1, PD2, and PD3), polyamine carboxylate demetallizers (i.e., PCD1, PCD2, and PCD3), and separation temperature on the removal of ferrum, calcium, sulfur, and nitrogen in medium- and low-temperature coal tar were determined. PD2 was selected, and the added amount was 200 µg·g-1. When the PD2 demulsifier was added alone or PD2 demulsifier with various demetallization agents was added, heteroatoms in coal tar could be effectively removed. For the experiments and analysis, the pretreatment conditions of coal tar were as follows: the addition amount of the PD2 demulsifier was 200 µg·g-1, the addition amount of the PCD3-type demetallization agent was 400 µg·g-1, and the stirring temperature was 80 °C. Before and after pretreatment, the methods of inductively coupled plasma-atomic emission spectrometer, gas chromatography-mass spectrometry (MS), and Fourier transform-ion cyclotron resonance MS were used in the present study to explore and analyze the distribution, occurrence form, and removal law of sulfur in coal tar. As revealed from the results, sulfur compounds in coal tar <360 °C fraction (light coal tar fraction, LF) before being pretreated had a lower content, which existed as benzothiophene and dibenzothiophene largely. Sulfur compounds S1 and S2 achieved the maximum relative abundance in >360 °C fraction (heavy coal tar fraction, HF). After the compounds were pretreated, the sulfur removal rate reached 40.0% in LF, and the sulfur compounds were primarily removed. For HF, the sulfur removal rate reached 20.1%. In addition, S1 compounds within the dibenzothiophene derivatives exhibiting more side chains and a larger condensation degree were basically removed. S2 compounds, mainly linked to several quinolines or more aromatic rings and thioether-aliphatic amine sulfur compounds exhibiting small molecular weight and simple structures, were relatively easy to remove. The SO class (e.g., the sulfones and thiophene-ketone group) was more difficult to remove.

Structure Characterization and Solubility Analysis of the Existent Gum of the Fischer-Tropsch Synthetic Crude.

The existent gum content of the Fisher-Tropsch synthetic crude exceeded the standard seriously, affecting its transportation and use. To determine the structure of the existent gum extracted from the Fisher-Tropsch synthetic crude, elemental analysis, Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR), and X-ray photoelectron spectroscopy (XPS) were employed to determine the chemical structure of the gum. The Brown-Ladner method is used to calculate the average structural parameters and the average molecular formula of the existent gum. The results show that the existent gum of the Fisher-Tropsch synthetic crude is composed of heterocyclic aromatic hydrocarbons and short-carbon paraffins. Compared with petroleum gums and coal tar gums, the existent gum content of the Fisher-Tropsch synthetic crude has the characteristics of high aromaticity, short side chains, and nitrogen-containing heterocycles. After being oxidized, its aromaticity further increases, more closed loops are formed, and the side chain is further shortened. This is caused by a complex oxidation reaction during the oxidation process. Molecular dynamics simulation calculations were performed to reveal the T-stacked morphology of the existent gum of the Fisher-Tropsch synthetic crude in a mixed solvent of acetone and toluene.

LvPPAE2 induced by WSV056 confers host defense against WSSV in Litopenaeus vannamei.

Viral immediate early (IE) genes encode regulatory proteins that are critical for viral replication. WSV056 is an IE protein of white spot syndrome virus (WSSV), an important pathogen of farmed shrimp. It targets the host Rb protein(s) and, according to a previous study, may enhance the replication of the viral genome. However, the ectopic expression of WSV056 in transgenic Drosophila melanogaster exerted an inhibitory effect on the replication of Drosophila C virus (DCV). Transcriptome study using Affymetrix GeneChip suggested that the enrichment of serine proteases (SPs) likely accounts for DCV inhibition in WSV056-overexpressing Drosophila. Injection of recombinant WSV056 to the WSSV natural host Litopenaeus vannamei enhanced the expression of the SP family member prophenoloxidase-activating enzyme 2 (LvPPAE2) and conferred shrimp with more resistance to WSSV infection. LvPPAE2 knockdown contributed to decreased expression of antimicrobial peptides LvAlf1 and LvLyz1, reduced hemolymph phenoloxidase activity, and increased virus load, suggesting that LvPPAE2 is involved in the host defense against WSSV infection. Taken together, these results suggest that wsv056 plays a role in restricting viral replication by inducing the SP-mediated immune responses in the host.