[Effects of hypoxia and acidification stress on ion regulation and gill structure of juvenile Larimichthys crocea.] / ä½Žæ°§åŠé ¸åŒ–èƒè¿«å¯¹å¤§é»„é±¼å¹¼é±¼ç¦»å­è°ƒèŠ‚ä¸Žé³ƒç»„ç»‡ç»“æž„çš„å½±å“.

To investigate the ion regulation of large yellow croaker (Larimichthys crocea) under hypoxia and acidification stresses, we investigated the effects of hypoxia (dissolved oxygen DO 3.5 mg·L-1, pH 8.1), acidification (DO 7.0 mg·L-1, pH 7.35) and combined stresses of hypoxia and acidification (DO 3.5 mg·L-1, pH 7.35) on gill tissue structure and physiological indices related to ion regulation of juvenile L. croaker. The results showed that, under hypoxia stress, gill Na+/K+-ATPase activity, serum Na+, Ca2+ and Cl- contents of juvenile L. croaker decreased first and then increased. Under acidification stress, gill Ca2+-ATPase activity, serum Na+ and Ca2+ contents of juvenile L. croaker increased first and then decreased. Under the combined stresses of hypoxia and acidification, Na+/K+-ATPase activity and Na+, K+ and Ca2+ contents increased first and then decreased, while Ca2+-ATPase activity and Cl- content decreased first and then increased. The results of gill histology showed that hypoxia and acidification stresses led to the detachment of gill epithelial cells, and the combined stresses of hypoxia and acidification led to proliferation, hypertrophy and swelling of gill epithelial cells. Comprehensive analysis showed that hypoxia and acidification stress affected the activities of major ion regulatory enzymes in juvenile L. croaker and caused different degrees of damage to gill tissue, resulting in imbalanced ion regulation in juvenile L. croaker.

Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins.

The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health1. The new coronavirus responsible for this outbreak-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG132. Although bats may be the reservoir host for a variety of coronaviruses3,4, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.

Structure-based identification of drug-like inhibitors of p300 histone acetyltransferase.

A growing body of evidence suggests that p300 histone acetyltransferase plays important roles in cancer cell differentiation and proliferation. Here, we employed structure-based hierarchical virtual screening method to identify novel lead compounds of p300 histone acetyltransferase. From a screening library containing approximate 100 000 diverse druglike compounds, 33 compounds were chosen for experimental testing and one compound, 4-acetyl-2-methyl-N-morpholino-3,4-dihydro-2H-benzo[b][1, 4]thiazine-7-sulfonamide (17), showed as micromolar inhibitor. Based on its predicted binding pose, we investigated its binding characteristics by designing two series of structural modifications. The obtained structure-activity relationship results are consistent with the predicted binding model. We expect that the identified novel p300 histone acetyltransferase inhibitors will serve as starting points for further development of more potent and specific histone acetyltransferase inhibitors.

[Effects of low salinity stress on the antioxidant enzyme activities in juvenile Pampus argenteus liver and the APTase activities in its gill and kidney].

By decreasing water salinity gradually, the Pampus argenteus juveniles were cultured at water salinity 25, 20, 15 and 10, for 24 h, 48 h, 96 h and 120 h, respectively, with the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (GST), and glutathione reductase (GR) in liver and the activities of Na+/K+- and Ga2+/Mg2+ -ATPase in gill and kidney determined. With the lowering of water salinity and the elongation of treated time, the liver SOD and GST activities had a trend of decreasing after an initial increase (P < 0.05), while the CAT activity was lower than the control except that it had a slight increase at salinity 20 cultured for 24 h and at salinity 15 cultured for 48 h (P < 0.05). The liver GPX activity had an increasing trend (P < 0.05), while the GR activity at salinity 15 cultured for 24 h increased first and then fell down to a relatively low level (P < 0.05). The Na+/K+ - and Ga2+/Mg2+-ATPase activities in the gill and kidney also decreased after an initial increase (P < 0.05), only the increase of ATPase activity at the thresholds of water salinity and treated time differed between the two organs. The results indicated that the decrease of water salinity could effectively stimulate and enhance the antioxidant enzyme activities in juvenile P. argenteus liver and the ATPase activities in its gill and kidney, and thereby, could effectively eliminate the excessive reactive oxygen species (ROS), sustain the intracellular homeostasis, and minimize the body damage. However, characterized by certain specificity and time sequentiality, the activation of test enzymes could also be inhibited when the salinity varied beyond the tolerance range of the body.

[Stringent RNA polymerase of E. coli and its in vivo transcriptional activity].

Several spontaneous E. coli mutants with the similar phenotype as that in the condition of amino acid deficiency were obtained on the selective media. One of the mutants (LCH001) showing slow growth phenotype on LB agar plate and pink or white colonies on MacConkey agar plate was mapped at rpoC gene encoding the beta' subunit of RNA polymerase by phage P1 transduction and transformation assays and found to be a new site mutation from G to T at 3406bp in the rpoC gene, which resulted in the amino acid change from Glycine (GGT) to Cysteine (TGT). The effect of the mutation on transcriptional activity of both stringent and non-stringent controlled promoters in vivo was measured by determining the beta-galactolactase activity of the growing cells. Results showed that the transcriptional activity of the mutant LCH001 reduced greatly on the stringent promoter, but increased significantly on the non-stringent promoter. The beta-galactolactase activity of the mutant LCH001 transcribed on stringent promoter was 18% lower, but 5-fold higher on the non-stringent controlled promoter than that of the wild-type strain CLT5034. This finding may give insights into future studies of the structure-function relationship of RNA polymerase as well as its role in the stringent response of bacteria.