Genome‐wide analysis of Nilaparvata lugens nymphal responses to high‐density and low‐quality rice hosts

The brown planthopper (BPH) Nilaparvata lugens is an economically important pest on rice plants. In this study, the higher population density and yellow‐ripe stage of rice plants were used to construct adverse survival conditions (ASC) against BPH nymphs. Simultaneously, the low population density and tillering stage of rice plants were used to establish a suitable survival condition (SSC) as a control. Solexa/Illumina sequencing was used to identify genes of BPH nymphs responding to ASC. Significantly longer duration development of BPH nymphs and significantly lower brachypterous ratio of BPH adults were observed by ASC compared with SSC. A total of 2 544 differentially expressed genes (DEGs) were obtained and analyzed by BLASTx, Gene Ontology and KEGG Orthology. Gene ontology analysis revealed that the DEGs were mainly involved in categories of cell, cell part, cellular process, binding, catalytic, organelle and metabolic processes. 1 138 DEGs having enzyme commission numbers were assigned to different metabolic pathways. The largest clusters were neurodegenerative diseases (137, 12.0%), followed by carbohydrate metabolism (113, 9.9%), amino acid metabolism (94, 8.3%), nucleotide metabolism (76, 6.7%), energy metabolism (64, 5.6%), translation (60, 5.3%), lipid metabolism (58, 5.1%), and folding, sorting and degradation (52, 4.6%). Expressing profile of 11 DEGs during eight nymphal developmental stages of BPH were analyzed by quantitative real‐time polymerase chain reaction. The 11 genes exhibited differential expression between ASC and SSC during at least one developmental stage. The DEGs identified in this study provide molecular proof of how BPH reconfigures its gene expression profile to adapt to overcrowding and low‐quality hosts.     

Effect of Reactive Oxygen Species Generation in Rabbit Corneal Epithelial Cells on Inflammatory and Apoptotic Signaling Pathways in the Presence of High Osmotic Pressure

It is generally accepted that high osmotic pressure (HOP) of lacrimal fluid is the core mechanism causing ocular inflammation and injury. However, the association between HOP and the regulation of cell inflammatory response and apoptotic pathways remains unclear. In the present study, we used HOP to interfere with in vitro cultured rabbit corneal epithelial cells, and found that HOP increased the generation of reactive oxygen species (ROS) in rabbit corneal epithelial cells, and increased ROS in turn induced the activation of JNK inflammatory signaling pathway, which further promoted the expression of pro-inflammatory factor NF-κβ and induced the generation of inflammatory factor IL-1β and TNF-α. In addition, HOP-induced ROS in rabbit corneal epithelial cells regulated the CD95/CD95L-mediated cell apoptotic signaling pathway by activating JNK inflammatory signaling pathway. These findings may serve as new theoretical basis and a new way of thinking about the treatment of ocular diseases, especially dry eye.     

Characteristic Steroids from the South China Sea Gorgonian Muricella sibogae and Their Cytotoxicities

Twenty‐four steroid‐based natural products, 9,10‐secosteroids ( 1 – 10 ), 1,4‐dien‐3‐one steroids ( 11 – 19 ), and 4‐en‐3‐one steroids ( 20 – 24 ), containing varying side‐chains, were isolated from the South China Sea gorgonian Muricella sibogae. The structures of one new 9,10‐secosteroid, sibogol D ( 1 ), and two new 1,4‐dien‐3‐one steroids, sibogols E and F ( 11 and 12 ), were elucidated by extensive spectroscopic analyses and by comparison with the literature data. Cytotoxicities for all the isolates were evaluated against four selected tumor cell lines, HL‐60, HCT116, K562, and P388. Compounds 3, 9 , and 13 exhibited potent cytotoxic activities against the HL‐60 cell line, with IC₅₀ values ranging from 1.27 to 10.05 μM , and compound 3 was also cytotoxic against HCT116 with an IC₅₀ value of 5.8 μM . The bioassay results also indicated a potential relationship between structural patterns and activity. The newly presented series of 1,4‐dien‐3‐one and 4‐en‐3‐one types of steroids relating to the unique 9,10‐secosteroids in biogenesis were found in this species for the first time, which is of considerable chemotaxonomic significance.     

Oceanic Distribution,Behaviour, and a Winter Aggregation Area of Adult Atlantic Sturgeon,Acipenser oxyrinchus oxyrinchus,in the Bay of Fundy,Canada

Seasonal distribution of adult Atlantic sturgeon was examined using pop-up satellite archival tags (PSATs) and ultrasonic transmitters deployed in the Saint John River, New Brunswick, Canada. Seven MK10 PSATs programmed for release in June 2012 and seven MiniPAT PSATs programmed for release in February and April 2013 were deployed in August 2011 and 2012, respectively. Eleven of 14 PSATs surfaced and transmitted depth and temperature data archived for the duration of their deployment (121–302 days). Among these eleven PSATs, five were recovered and 15-sec archival data was downloaded. Following exit from the Saint John River in the fall, tagged fish occupied a mean monthly depth of 76.3–81.6 m at temperatures as low as 4.9˚C throughout the winter before returning to shallower areas in the spring. The majority of ultrasonic detections occurred in the Bay of Fundy, but fish were detected as far as Riviere Saint-Jean, Quebec, approximately 1500 km from the Bay of Fundy (representing long-distance migratory rates of up to 44 km/day). All PSATs were first detected in the Bay of Fundy. Tags that released in February and April were found 5–21 km offshore of the Saint John Harbour, while tags that released in June were first detected in near shore areas throughout the Bay of Fundy. The substrate at winter tag release locations (estimated from backward numerical particle-tracking experiments) consisted primarily of moraines and postglacial mud substrate with low backscatter strength, indicative of soft or smooth seabed. Based on the proximity of winter tag release locations, the consistent depths observed between fish, and previous research, it is suspected that a winter aggregation exists in the Bay of Fundy. This study expands the understanding of the marine distribution and range of Atlantic sturgeon on the east coast of Canada.     

Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons

Increasing evidence shows that oxidative stress and the hyperphosphorylation of tau protein play essential roles in the progression of Alzheimer’s disease (AD). Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti-inflammatory properties. We investigated the neuroprotective effects of quercetin to HT22 cells (a cell line from mouse hippocampal neurons). We found that Okadaic acid (OA) induced the hyperphosphorylation of tau protein at Ser199, Ser396, Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative stress suppressed the cell viability and decreased the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), mitochondria membrane potential (MMP) and Glutathione peroxidase (GSH-Px). It up-regulated malondialdehyde (MDA) production and intracellular reactive oxygen species (ROS). In addition, phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3β (PI3K/Akt/GSK3β) and mitogen activated protein kinase (MAPK) were also involved in this process. We found that pre-treatment with quercetin can inhibited OA-induced the hyperphosphorylation of tau protein and oxidative stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but also via the inhibition of PI3K/Akt/GSK3β, MAPKs and activation of NF-κB p65. Our findings suggest the therapeutic potential of quercetin to treat AD.     

Prolonged Cerebral Circulation Time Is the Best Parameter for Predicting Vasospasm during Initial CT Perfusion in Subarachnoid Hemorrhagic Patients

Purpose

We sought to imitate angiographic cerebral circulation time (CCT) and create a similar index from baseline CT perfusion (CTP) to better predict vasospasm in patients with subarachnoid hemorrhage (SAH).

Methods

Forty-one SAH patients with available DSA and CTP were retrospectively included. The vasospasm group was comprised of patients with deterioration in conscious functioning and newly developed luminal narrowing; remaining cases were classified as the control group. The angiography CCT (XA-CCT) was defined as the difference in TTP (time to peak) between the selected arterial ROIs and the superior sagittal sinus (SSS). Four arterial ROIs were selected to generate four corresponding XA-CCTs: the right and left anterior cerebral arteries (XA-CCT_RA2 and XA-CCT_LA2) and right- and left-middle cerebral arteries (XA-CCT_RM2 and XA-CCT_LM2). The CCTs from CTP (CT-CCT) were defined as the differences in TTP from the corresponding arterial ROIs and the SSS. Correlations of the different CCTs were calculated and diagnostic accuracy in predicting vasospasm was evaluated.

Results

Intra-class correlations ranged from 0.96 to 0.98. The correlations of XA-CCT_RA2, XA-CCT_RM2, XA-CCT_LA2, and XA-CCT_LM2 with the corresponding CT-CCTs were 0.64, 0.65, 0.53, and 0.68, respectively. All CCTs were significantly prolonged in the vasospasm group (5.8–6.4 s) except for XA-CCT_LA2. CT-CCT_A2 of 5.62 was the optimal cut-off value for detecting vasospasm with a sensitivity of 84.2% and specificity 82.4%

Conclusion

CT-CCTs can be used to interpret cerebral flow without deconvolution algorithms, and outperform both MTT and TTP in predicting vasospasm risk. This finding may help facilitate management of patients with SAH.     

Clinical Validation of Therapeutic Drug Monitoring of Imipenem in Spent Effluent in Critically Ill Patients Receiving Continuous Renal Replacement Therapy: A Pilot Study

ObjectivesThe primary objective of this pilot study was to investigate whether the therapeutic drug monitoring of imipenem could be performed with spent effluent instead of blood sampling collected from critically ill patients under continuous renal replacement therapy.MethodsA prospective open-label study was conducted in a real clinical setting. Both blood and effluent samples were collected pairwise before imipenem administration and 0.5, 1, 1.5, 2, 3, 4, 6, and 8 h after imipenem administration. Plasma and effluent imipenem concentrations were determined by reversed-phase high-performance liquid chromatography with ultraviolet detection. Pharmacokinetic and pharmacodynamic parameters of blood and effluent samples were calculated.ResultsEighty-three paired plasma and effluent samples were obtained from 10 patients. The Pearson correlation coefficient of the imipenem concentrations in plasma and effluent was 0.950 (P<0.0001). The average plasma-to-effluent imipenem concentration ratio was 1.044 (95% confidence interval, 0.975 to 1.114) with Bland-Altman analysis. No statistically significant difference was found in the pharmacokinetic and pharmacodynamic parameters tested in paired plasma and effluent samples with Wilcoxon test.ConclusionSpent effluent of continuous renal replacement therapy could be used for therapeutic drug monitoring of imipenem instead of blood sampling in critically ill patients.     

EXPRESSION AND EFFECTS OF MUTANT Bombyx mori ACETYLCHOLINESTRASE1 IN BmN CELLS

The main mechanism of toxicity of organophosphate (OP) and carbamate (CB) insecticides is their irreversible binding and inhibition of acetylcholinestrase (AChE), encoded by ace1 (acetylcholinestrase gene 1), leading to eventual death of insects. Mutations in AChE may significantly reduce insects susceptibility to these pesticides. Bombyx mori is an important beneficial insect, and no OP‐ or CB‐resistant strains have been generated. In this study, wild‐type ace1 (wace1) and mutant ace1 (mace1) were introduced into BmN cells, confirmed by screening and identification. The expression of wace1 and mace1 in the cells was confirmed by Western blot and their expression levels were about 21‐fold higher than the endogenous ace1 level. The activities of AChE in wace1 and mace1 transgenic cells were 10.6 and 20.2% higher compared to control cells, respectively. mace1 transgenic cells had higher remaining activity than wace1 transgenic cells under the treatment of physostigmine (a reversible cholinesterase inhibitor) and phoxim (an OP acaricide). The results showed that ace1 transgene can significantly improve ace1 expression, and ace1 mutation at a specific site can reduce the sensitivity to AChE inhibitors. Our study provides a new direction for the exploration of the relationship between AChE mutations and drug resistance.