Binding properties of chemosensory protein 4 in Riptortus pedestris to aggregation pheromones.

In insects, chemosensory proteins (CSPs) play an important role in the perception of the external environment and have been widely used for protein-binding characterization. Riptortus pedestris has received increased attention as a potential cause of soybean staygreen syndrome in recent years. In this study, we found that RpedCSP4 expression in the antennae of adult R. pedestris increased with age, with no significant difference in expression level observed between males and females, as determined through quantitative real-time polymerase chain reaction (qRT-PCR). Subsequently, we investigated the ability of RpedCSP4 to bind various ligands (five aggregated pheromone components and 13 soybean volatiles) using a prokaryotic expression system and fluorescence competitive binding assays. We found that RpedCSP4 binds to three aggregated pheromone components of R. pedestris, namely, ((E)-2-hexenyl (Z)-3-hexenoate (E2Z3), (E)-2-hexenyl (E)-2-hexenoate (E2E2), and (E)-2-hexenyl hexenoate (E2HH)), and that its binding capacities are most stable under acidic condition. Finally, the structure and protein-ligand interactions of RpedCSP4 were further analyzed via homology modeling, molecular docking, and targeted mutagenesis experiments. The L29A mutant exhibited a loss of binding ability to these three aggregated pheromone components. Our results show that the olfactory function of RpedCSP4 provides new insights into the binding mechanism of RpedCSPs to aggregation pheromones and contributes to discover new target candidates that will provide a theoretical basis for future population control of R. pedestris.

Binding properties of chemosensory protein 12 in Riptortus pedestris to aggregation pheromone (E)-2-hexenyl (Z)-3-hexenoate.

Riptortus pedestris (bean bug), a common soybean pest, has a highly developed olfactory system to find hosts for feeding and oviposition. Chemosensory proteins (CSPs) have been identified in many insect species; however, their functions in R. pedestris remain unknown. In this study, quantitative real time-polymerase chain reaction (qRT-PCR) revealed that the expression of RpedCSP12 in the adult antennae of R. pedestris increased with age. Moreover, a significant difference in the expression levels of RpedCSP12 was observed between male and female antennae at one and three days of age. We also investigated the binding ability of RpedCSP12 to different ligands using a prokaryotic expression system and fluorescence competitive binding assays. We found that RpedCSP12 only bound to one aggregation pheromone, (E)-2-hexenyl (Z)-3-hexenoate, and its binding decreased with increasing pH. Furthermore, homology modelling, molecular docking, and site-directed mutagenesis revealed that the Y27A, L74A, and L85A mutants lost their binding ability to (E)-2-hexenyl (Z)-3-hexenoate. Our findings highlight the olfactory roles of RpedCSP12, providing insights into the mechanism by which RpedCSPs bind to aggregation pheromones. Therefore, our study can be used as a theoretical basis for the population control of R. pedestris in the future.

Serum level of macrophage migration inhibitory factor predicts severity and prognosis in patients with ischemic stroke.

OBJECTIVE: To evaluate whether the macrophage migration inhibitory factor (MIF) level in serum of ischemic stroke patients was associated with their clinical severity and early outcome. METHODS: During February 2017-March 2018, consecutive patients admitted to our hospital because of first-ever ischemic stroke were identified. The prognostic value of MIF was set for predicting the outcome of these patients at discharge. The results were compared with existing methods, including National Institutes of Health Stroke Scale (NIHSS) score and validated indicators. RESULTS: 289 patients were enrolled. The serum level of all patients was determined (median: 20.6 ng/ml). At admission, 131 patients (45.3%) were evaluated as minor stroke (NIHSS < 5). When serum level of MIF was increased by each 1 ng/ml, the unadjusted and adjusted risk of moderate-to-high clinical severity was elevated by 5% (OR = 1.05 [95% CI: 1.01-1.09], P = 0.006) and 3% (1.03 [1.00-1.08], P = 0.02), respectively. At discharge, 82 patients (28.4%) had poor functional outcomes. The median serum level of MIF was lower in group with good outcomes than that observed in poor outcomes (19.4[15.8-24.2] vs. 24.0[19.9-29.4] ng/ml; P < 0.001). When serum level of MIF was increased by each 1 ng/ml, the unadjusted and adjusted risk of poor outcomes was elevated by 9% (1.09 [1.05-1.13], P < 0.001) and 6% (1.06 [1.02-1.10], P < 0.01), respectively. CONCLUSIONS: High MIF levels are independently related to the moderate to high clinical severity in ischemic stroke patients, as well as the poor outcome at discharge.

Genome-Wide Analysis of Odorant-Binding Proteins and Chemosensory Proteins in the Bean bug Riptortus pedestris.

Insects have sensitive olfactory systems to interact with environment and respond to the change in host plant conditions. Key genes in the system can be potential targets for developing new and efficient pest behaviour control methods. Riptortus pedestris is an important soybean pest in East Asia and has caused serious damage to the soybean plants in Huang-Huai-Hai region of China. However, the current treatment of pests is dominated by chemical insecticides and lacks efficient sustainable prevention and control technologies. In this study, we identified 49 putative odorant-binding proteins (OBPs) (43 were new genes) and 25 chemosensory proteins (CSPs) (17 were new genes) in R. pedestris genome. These OBP and CSP genes are clustered in highly conserved groups from other hemipteran species in phylogenetic trees. Most RpedOBPs displayed antennal-biased expression. Among the 49 RpedOBPs, 33 were significantly highly expressed in the antennae, including three male-biased and nine female-biased. While many RpedCSPs were detected both in the antennae and in non-antennal tissues, only 11 RpedCSPs displayed antennal-biased expression, in which four RpedCSPs were male-biased and five RpedCSPs were female-biased. Some OBP and CSP genes showed sex-biased expression profiles. Our results not only provide a foundation for future exploration of the functions of RpedOBPs and RpedCSPs but also aid in developing environmentally friendly insecticides in the future.

Systematic Review and Meta-Analysis of the Efficacy of Appropriate Empiric Anti-Enterococcal Therapy for Intra-Abdominal Infection.

Background: Delayed treatment of seriously infected patients results in increased mortality. However, antimicrobial therapy for the initial 24 to 48 hours is mostly empirically provided, without evidence regarding the causative pathogen. Whether empiric anti-enterococcal therapy should be administered to treat intra-abdominal infection (IAI) before obtaining culture results remains unknown. We performed a meta-analysis to explore the effects of empiric enterococci covered antibiotic therapy in IAI and the risk factors for enterococcal infection in IAI. Methods: We searched multiple databases systematically and included 23 randomized controlled trials (RCTs) and 13 observational studies. The quality of included studies was assessed, and the reporting bias was evaluated. Meta-analysis was performed using random effects or fixed effects models according to the heterogeneity. The risk ratio (RR), odds ratio (OR), and 95% confidence interval (CI) were calculated. Results: Enterococci-covered antibiotic regimens provided no improvement in treatment success compared with control regimens (RR, 0.99; 95% CI, 0.97-1.00; p = 0.15), with similar mortality and adverse effects in both arms. Basic characteristic analysis revealed that most of the enrolled patients with IAI in RCTs were young, lower risk community-acquired intra-abdominal infection (CA-IAI) patients with a relatively low APACHE II score. Interestingly, risk factor screening revealed that malignancy, corticosteroid use, operation, any antibiotic treatment, admission to intensive care unit (ICU), and indwelling urinary catheter could predispose the patients with IAI to a substantially higher risk of enterococcal infection. "Hospital acquired" itself was a risk factor (OR, 2.81; 95% CI, 2.34-3.39; p < 0.001). Conclusion: It is unnecessary to use additional agents empirically to specifically provide anti-enterococcal coverage for the management of CA-IAI in lower risk patients without evidence of causative pathogen, and risk factors can increase the risk of enterococcal infection. Thus, there is a rationale for providing empiric anti-enterococcal coverage for severely ill patients with CA-IAI with high risk factors and patients with hospital-acquired intra-abdominal infection (HA-IAI).

Aspirin resistance predicts unfavorable functional outcome in acute ischemic stroke patients.

OBJECTIVE: To investigate the prognostic value of aspirin reaction units (ARU) in a 3-month follow-up study in a cohort of Chinese patients with first-ever ischemic stroke. METHODS: Prospective single-center survey of acute ischemic stroke patients receiving aspirin therapy. Two hundred and seventy-five Chinese patients with first-ever ischemic stroke who previously received aspirin therapy were enrolled. ARU was measured using the VerifyNow system. A cutoff of 550 ARU was used to determine the presence of aspirin resistance (AR). RESULTS: Median age at study entry was 67 years (IQR: 59-75) and 142(51.6%) were male. A total of 52 of 275 enrolled patients (18.9%) were AR. Median regression estimated a statistically significant increase in NIHSS score of 0.033 point for every 1-point increase in ARU (95% CI, 0.024 to 0.068; P < 0.001). The unfavorable outcomes distribution across the ARU quartiles ranged between 11.8% (first quartile) to 64.8% (fourth quartile). After adjusting for other established risk factors, in multivariate models comparing the third and fourth quartiles against the first quartile of the ARU, levels of ARU were associated with unfavorable outcome, and the adjusted risk of unfavorable outcome increased by 145% (OR = 2.45 [95% CI 1.46-3.87], P = 0.011) and 317% (4.17[2.76-6.15], P < 0.001), respectively. Similarly, the adjusted risk of mortality increased by 215% (OR = 3.15 [95% CI 1.98-4.73], P = 0.008) and 429% (5.29[4.02-8.17], P < 0.001), respectively. CONCLUSIONS: The results suggest that AR is a meaningful and independent marker to predict short-term functional outcome in patients with ischemic stroke.

An Increased Serum Level of Lipoprotein(a) Is a Predictor for Deep Vein Thrombosis in Patients with Spinal Cord Injuries.

OBJECTIVE: This prospective cohort-designed study was performed to verify whether higher levels of serum lipoprotein(a) (Lp(a)) could be a risk factor for deep vein thrombosis (DVT) in Chinese patients with spinal cord injuries (SCI). METHODS: During 2013-2014, consecutive patients with first-ever SCI were recruited and assessed for DVT using color Doppler ultrasonography for 15 days after injury and whenever clinically requested. Using logistic regression models, multivariate analyses were performed. Receiver operating characteristic curves tested the overall predicted accuracy of Lp(a) and other markers. RESULTS: In this study, 358 patients were screened in the analysis, and 279 patients with SCI were included and completed the 15-day follow-up. Fifty-five patients (19.7%) were diagnosed with DVT. Patients with SCI with DVT had significantly higher Lp(a) levels on admission (554 mg/L [interquartile range, 416-790 mg/L] vs. 158 mg/L [interquartile range, 72-252 mg/L]; P < 0.0001). Adjusted for common risk factors, multivariate analyses showed that serum Lp(a) ≥ 300 mg/L could be used independently to predict DVT (odds ratio, 10.35; 95% confidence interval [CI], 2.37-45.35; P < 0.0001). With an area under the curve (AUC) of 0.91 (95% CI, 0.86-0.94), Lp(a) showed a significantly greater discriminatory ability in predicting DVT compared with high-sensitivity C-reactive protein (AUC, 0.81; 95% CI, 0.74-0.88; P < 0.01), homocysteine (AUC, 0.78; 95% CI, 0.71-0.84; P < 0.01) and age (AUC, 0.66; 95% CI, 0.59-0.73; P < 0.001). CONCLUSIONS: Increased serum Lp(a) levels were independent predictors of DVT in patients with SCI in China, suggesting a possible role of Lp(a) in the pathogenesis of DVT.

Plasma levels of copeptin predict 1-year mortality in patients with acute ischemic stroke.

To evaluate the association between plasma levels of copeptin and 1-year mortality in a cohort of Chinese patients with acute ischemic stroke. We prospectively studied 275 patients with ischemic stroke who were admitted within 24 h after the onset of symptoms. Copeptin and NIH stroke scale (NIHSS) score were measured at the time of admission. The prognostic value of copeptin to predict mortality within 1 year was compared with the NIHSS score and other known outcome predictors. Nonsurvivors had significantly higher copeptin levels on admission compared with survivors (P<0.0001). Multivariate logistic regression analysis showed that elevated plasma levels of copeptin were an independent stroke mortality predictor, with an adjusted odds ratio of 4.48 [95% confidence interval (CI), 2.18-9.06]. The area under the receiver operating characteristic curve of copeptin was 0.882 (95% CI, 0.847-0.921) for stroke mortality, which yielded a sensitivity of 90.7% and a specificity of 84.5%. Copeptin improved the NIHSS score (area under the curve of the combined model, 0.94; 95% CI, 0.91-0.97; P=0.011). Elevated plasma copeptin levels at admission were an independent predictor of long-term mortality after ischemic stroke in a Chinese sample, suggesting that these alterations might play a role in the pathophysiology of stroke.

Executive dysfunction in patients with cerebral hypoperfusion after cerebral angiostenosis/occlusion.

Impairment of executive functions (EFs) was investigated in patients with cerebral hypoperfusion after cerebral angiostenosis/occlusion. Several EFs were measured in patients with cerebral angiostenosis/occlusion and healthy subjects. The vascular conditions, regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), mean transit time (MTT), time to peak (TTP), and delay time were assessed. The scores of the vascular stenosis/occlusion group were significantly lower than those of the control group. rCBV and rCBF were negatively correlated with the error response times in the Stroop test, and the persistent error responses in the Wisconsin Card Sorting Test (WCST) were positively correlated with the Montreal Cognitive Assessment (MoCA) scores. TTP was positively correlated with the reaction and error reaction times, and the persistent error response in WCST was negatively correlated with the times of sorting in WCST and MoCA scores. MTT was positively correlated with the persistent error response in WCST. In the Stroop test, delay time was positively correlated with response time, and negatively correlated with error response times, and the persistent error response in WCST and MoCA scores. Patients with cerebral hypoperfusion after cerebral angiostenosis/occlusion had executive dysfunctions in working memory, sustained attention, response inhibition, cognitive flexibility, thought organization, planning, and implementation. Moreover, their executive dysfunctions were related with the decline in rCBF and rCBV. The prolonged TTP, MTT, and delay time suggested a slow blood flow and the poor compensation of collateral circulation, resulting in impairment of the EFs.