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An efficient method for the construction of benzo[4,5]imidazo[1,2- a ]pyrimidines using N , N -dimethylformamide as a one-carbon source and 2-aminobenzimidazoles and acetophenone as substrates through a one-pot, three-component cascade reaction is described. Spectra investigations indicated the fluorescent properties of selected products, exhibiting quantum yields 0.07-0.16 with maxima absorption at 266-294 nm and emission at 472-546 nm.

Hydrogen sulfide (H 2 S) is a common toxic gas in chicken houses that endangers the health of poultry. Harbin has a cold climate in winter, and the conflict between heat preservation and ventilation in poultry houses is obvious. In this study, we investigated the H 2 S content in chicken houses during winter in Harbin and found that the H 2 S concentration exceeded the national standard in individual chicken houses. Then, a model of H 2 S exposure was established in an environmental simulation chamber. We also developed a NaHS exposure model of chicken peripheral blood lymphocytes in vitro. Proteomics analysis was used to reveal the toxicology of thymus injury in broilers, the FOXO signaling pathway was determined to be significantly enriched, ROS bursts and JNK/MST1/FOXO1 pathway activation induced by H 2 S exposure were detected, and ROS played an important switch role in the JNK/MST1/FOXO1 pathway. In addition, H 2 S exposure-induced thymus cell death involved immune dysregulation. Overall, the present study adds data for H 2 S contents in chicken houses, provides new findings for the mechanism of H 2 S poisoning and reveals a new regulatory pathway in immune injury., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Atmospheric hydrogen sulfide (H 2 S) is a highly toxic air pollutant that has a negative effect on human health and animal welfare. The immunotoxicity of H 2 S has been explored previously, but its mechanism still needs to be clarified, especially in chickens. To further evaluate the immunotoxicity of H 2 S, 1-day-old broilers were recruited and exposed to atmospheric H 2 S for 42 days of age. Our results showed that H 2 S significantly reduced the thymus index and the CD4 + and CD8 + T-lymphocyte numbers and that it also changed the CD4 + /CD8 + ratio. The morphological analysis showed that H 2 S incrassated the medulla and generated inflammatory infiltration. In addition, it caused the mitochondria to swell and the chromatin to condense, and destroyed nuclear structures were observed. We also conducted bioinformation and transcriptomic analyses to delve the mechanism of H 2 S toxicity in chicken thymus. We measured 172 differently expression genes (DEGs) after H 2 S exposure and further filtrated the DEGs that are related to inflammation and cell death that play a critical role in immune function. We concluded that H 2 S significantly increased IL-1β, IL-4 and IL-10 levels, whereas it downregulated IL-12 and IFN-γ. This study confirmed that H 2 S triggered the thymus inflammatory response and caused a Th1/Th2 imbalance. Moreover, our results demonstrated that H 2 S triggered the TLR-7/MyD88/NF-κB pathway to promote NLRP3 inflammasome activation. In conclusion, atmospheric H 2 S actives the TLR-7/MyD88/NF-κB pathway and the NLRP3 inflammasome to promote an inflammatory response, which then causes tissues damage in broiler thymus. These results provide new insights for unveiling the immunotoxic effects of H 2 S., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Hydrogen sulfide (H 2 S) is one of the main pollutants in the atmosphere, which is a serious threat to human health. The decomposition of sulfur-containing organics in chicken houses could produce a large amount of H 2 S, thereby damaging poultry health. In this study, one-day-old broilers were selected and exposed to 4 or 20 ppm of H 2 S gas (0-3 weeks: 4 ± 0.5 ppm, 4-6 weeks: 20 ± 0.5 ppm). The spleen samples were collected immediately after the chickens were euthanized at 2, 4, and 6 weeks. The histopathological and ultrastructural observations showed obvious necrosis characteristics of H 2 S-exposed spleens. H 2 S exposure suppressed GSH, CAT, T-AOC, and SOD activities; increased NO, H 2 O 2 , and MDA content and iNOS activity; and induced oxidative stress. ATPase activities and the expressions of energy metabolism-related genes were significantly decreased. Also, the expressions of related necroptosis (RIPK1, RIPK3, MLKL, TAK1, TAB2, and TAB3) were significantly increased, and the MAPK pathway was activated. Besides, H 2 S exposure activated the NF- κ B classical pathway and induced TNF- α and IL-1 β release. Taken together, we conclude that H 2 S exposure induces oxidative stress and energy metabolism dysfunction; evokes necroptosis; activates the MAPK pathway, eventually triggering the NF- κ B pathway; and promotes inflammatory response in chicken spleens., Competing Interests: The authors declare that they have no conflict of interest.

Objective: To study the pharmacokinetics and bioequivalence of asparaginase loaded in hyaluronic acid-graft-poly(ethylene glycol)/ sulfobutylether-β-cyclodextrin nanocapsules (AHSP) in SD rats., Methods: The morphology of AHSP was observed under the transmission electron microscope and the particle size and zeta potential were measured. AHSP and free asparaginase were intravenously injected in rats, and the plasma asparaginase activity was measured at different time points after the injections. The pharmacokinetic parameters were calculated using the software DAS 2.1.1 to assess the bioequivalence of AHSP and free asparaginase., Results: AHSP had an average particle size of 413.80∓10.97 nm with a zeta potential of -20.37∓2.38 mV. The AUC(0-48 h) of AHSP and free asparaginase was 137.34∓1.82 U/mL and 46.38 ∓1.98 U/mL, and their AUC(0-∞) was 164.66∓6.88 U/mL and 51.44∓3.01 U/mL with half-lives of 4.62∓0.60 h and 1.86∓0.38 h, respectively. Compared with free AN, AHSP exhibited increased AUC(0-48 h), AUC(0-∞), and half-life by 2.24, 2.55 and 2.32 folds, respectively. The 90% confidential intervals of AUC(0-48 h), AUC(0-∞) and Cmax of the tested formulation were 75.0%-76.5%, 74.3%-76.1%, and 95.1%-96.7%, respectively., Conclusion: AHSP can improve the bioavailability and extend the biological half-life of asparaginase in rats, and AHSP and free asparaginase are not bioequivalent.

Objective: To study the effects on the survival rates and DNA damage of benzo[a]pyrene or lead alone or in combination in rat neurons in vivo., Methods: Primary cultures of rat cerebellar neurons were prepared from 8-day-old pups, 10 groups cultures in each experiments were used, (1) control group, (2) vehicle group (Equal volume of DMSO + S9-mix), (3) low dose lead group (PbAc 5 micromol/L), (4) high dose lead group (PbAc 50 micromol/L), (5) low dose BaP group (BaP 5 micromol/L+ S9-mix), (6) high dose BaP group (BaP 50 micromol/L + S9-mix), (7) low dose lead + low dose BaP group, (8) low dose lead + high dose BaP group, (9) high dose lead + low dose BaP group, (10) high dose lead + high dose BaP group. After 90 min administration, the neurons were collected by the method of trypsin digestion, the survival rates were detected by the method of Tapian-blue dying, Detect cracks on the DNA straps by the method of SCGE., Results: (1) The survival rates of all the administrated groups were significantly lower than that of control groups (P < 0.05, P < 0.01). (2) In the high-dose BaP group (group 6), groups combine administrated with BaP and lead, one or two of them at high dose (groups 8, 9, 10), the DNA damage were more serious than that of control groups (P < 0.01)., Conclusion: (1) Both BaP and lead with some vivo neurotoxicity, the effects of two toxicants can do concord. (2) Neuron DNA damage may be one of the mechanisms by which BaP result in toxicity on the cultured neurons.