Differential gene expression in response to eCry3.1Ab ingestion in an unselected and eCry3.1Abselected western corn rootworm (Diabrotica virgifera virgifera LeConte) population

Diabrotica virgifera virgifera LeConte, the western corn rootworm (WCR) is one of the most destructive pests in the U.S. Corn Belt. Transgenic maize lines expressing various Cry toxins from Bacillus thuringiensis have been adopted as a management strategy. However, resistance to many Bt toxins has occurred. To investigate the mechanisms of Bt resistance we carried out RNA-seq using Illumina sequencing technology on resistant, eCry3.1Ab-selected and susceptible, unselected, whole WCR neonates which fed on seedling maize with and without eCry3.1Ab for 12 and 24 hours. In a parallel experiment RNA-seq experiments were conducted when only the midgut of neonate WCR was evaluated from the same treatments. After de novo transcriptome assembly we identified differentially expressed genes (DEGs). Results from the assemblies and annotation indicate that WCR neonates from the eCry3.1Ab-selected resistant colony expressed a small number of up and down-regulated genes following Bt intoxication. In contrast, unselected susceptible WCR neonates expressed a large number of up and down-regulated transcripts in response to intoxication. Annotation and pathway analysis of DEGs between susceptible and resistant whole WCR and their midgut tissue revealed genes associated with cell membrane, immune response, detoxification, and potential Bt receptors which are likely related to eCry3.1Ab resistance. This research provides a framework to study the toxicology of Bt toxins and mechanism of resistance in WCR, an economically important coleopteran pest species

Socioeconomic Status and the Quality of Acute Stroke Care

Background and Purpose—The association of socioeconomic status (SES) with quality of stroke care is not well understood, and few studies have examined the association with different indicators of SES simultaneously. We assessed the impacts of low levels of education, occupation, and income on the quality of stroke care. Methods—We examined data from the China National Stroke Registry recording consecutive stroke patients between September 2007 and August 2008. Baseline low SES was measured using educational level <6 years, occupation as manual workers or no job, and average family income per capita at ≤¥1000 per month. Compliance with 11 performances was summarized in a composite score defined as the proportion of all needed care given. Poor quality of care was defined as having a composite score of 0.71 or less. Results—Among 12 270 patients with ischemic stroke, 38.6% had <6 educational years, 37.6% had manual workers/no job, and 34.7% had income ≤¥1000 per month. There was an increased chance of receiving poor quality of care in patients with low education (adjusted odds ratio 1.15, 95% confidence interval 1.03–1.28), low occupation (adjusted odds ratio 1.16, 95% confidence interval 1.01–1.32), and low income (adjusted odds ratio 1.18, 95% confidence interval 1.06–1.30), respectively. People with low SES had poor performances on some aspects of care quality. Combined effects existed among these SES indicators; those with low SES from all 3 indicators had the poorest quality of care. Conclusions—There was a social gradient in the quality of stroke care. Continuous efforts of socioeconomic improvement will increase the quality of acute stroke care.The Ministry of Science and Technology of the People’s Republic of China (2006BAI01A11, 2011BAI08B01, 2011BAI08B02, 2012ZX09303-005-001, and 2013BAI09B03), The Beijing Biobank of Cerebral Vascular Disease (D131100005313003), Beijing Institute for Brain Disorders (BIBD-PXM2013_014226_07_000084

An Organic–Inorganic Hybrid Cathode Based on S–Se Dynamic Covalent Bonds

A diphenyl trisulfide–selenium nanowire (DPTS‐Se) organic–inorganic hybrid cathode material is presented for rechargeable lithium batteries. During discharge, three voltage plateaus associated with three lithiation processes are observed. During recharge, the combination of the radicals formed upon delithiation leads to several new phenyl sulfoselenide compounds which are confirmed by HPLC‐QTof‐MS. The hybrid cathode exhibits superior cycling stability over pristine Se or DPTS as cathode alone. The first discharge shows a capacity of 96.5 % of the theoretical specific capacity and the cell retains 69.2 % of the initial capacity over 250 cycles. The hybrid cathode also shows a high Coulombic efficiency of over 99 % after 250 cycles. This study demonstrates that the combination of organic polysulfide and selenium can not only improve the utilization of active materials but also enhance the cycling performance

Platelet Count Predicts Adverse Clinical Outcomes After Ischemic Stroke or TIA: Subgroup Analysis of CNSR II

Background: The clinical significance of platelet count (PC) for ischemic cerebrovascular disease is not well-established and further risk stratification according to baseline PC within normal range has not been reported before. We aim to evaluate the prognostic effect of baseline circulating PC within normal range on the risk of long-term recurrent stroke, mortality and functional outcomes after ischemic stroke or TIA.Methods: We derived data from eligible patients with ischemic stroke or TIA from the China National Stroke Registry (CNSR) II. Participants were divided into quintiles according to baseline PC within normal range (100–450 × 109/L). Multivariable cox regression and logistic regression were adopted to explore the correlation of baseline PC with recurrent stroke, mortality and poor functional outcomes (modified Rankin Scale 3~6) within 1-year follow-up.Results: Among the16842 eligible participants, the average age was 64.7 ± 11.9, 1,241 (7.4%) had recurrent stroke, 1,377 (8.2%) died, and 3,557 (21.1%) ended up with poor functional outcomes after 1-year follow-up. Compared with the third PC quintile (186–212 × 109/L), patients in the top quintile (249–450 × 109/L) presented with increased risk of recurrent stroke (adjusted hazard ratio 1.21, [1.02–1.45]), all-cause mortality (adjusted hazard ratio 1.43, [1.19–1.73]), and poor functional outcome (adjusted odds ratio 1.49, [1.28–1.74]), while patients in the lowest PC quintile(100–155 × 109/L) had higher risk of poor functional outcome (adjusted odds ratio 1.19, [1.02–1.38]).Conclusion: In ischemic stroke or TIA patients with platelet count within normal range, platelet count may be a qualified predictor for long-term recurrent stroke, mortality, and poor functional outcome

Substantial Progress Yet Significant Opportunity for Improvement in Stroke Care in China

BACKGROUND AND PURPOSE: Stroke is a leading cause of death in China. Yet the adherence to guideline-recommended ischemic stroke performance metrics in the past decade has been previously shown to be suboptimal. Since then, several nationwide stroke quality management initiatives have been conducted in China. We sought to determine whether adherence had improved since then. METHODS: Data were obtained from the 2 phases of China National Stroke Registries, which included 131 hospitals (12 173 patients with acute ischemic stroke) in China National Stroke Registries phase 1 from 2007 to 2008 versus 219 hospitals (19 604 patients) in China National Stroke Registries phase 2 from 2012 to 2013. Multiple regression models were developed to evaluate the difference in adherence to performance measure between the 2 study periods. RESULTS: The overall quality of care has improved over time, as reflected by the higher composite score of 0.76 in 2012 to 2013 versus 0.63 in 2007 to 2008. Nine of 13 individual performance metrics improved. However, there were no significant improvements in the rates of intravenous thrombolytic therapy and anticoagulation for atrial fibrillation. After multivariate analysis, there remained a significant 1.17-fold (95% confidence interval, 1.14-1.21) increase in the odds of delivering evidence-based performance metrics in the more recent time periods versus older data. The performance metrics with the most significantly increased odds included stroke education, dysphagia screening, smoking cessation, and antithrombotics at discharge. CONCLUSIONS: Adherence to stroke performance metrics has increased over time, but significant opportunities remain for further improvement. Continuous stroke quality improvement program should be developed as a national priority in China

Clopidogrel with aspirin in High-risk patients with Acute Non-disabling Cerebrovascular Events II (CHANCE-2): rationale and design of a multicenter randomised trial

Background: In patients with a minor ischaemic stroke or transient ischaemic attack (TIA), separate trials have shown that dual antiplatelet therapy with clopidogrel plus aspirin (clopidogrel–aspirin) or ticagrelor plus aspirin (ticagrelor–aspirin) are more effective than aspirin alone in stroke secondary prevention. However, these two sets of combination have not been directly compared. Since clopidogrel was less effective in stroke patients who were CYP2C19 loss-of-function (LOF) allele carriers, whether ticagrelor–aspirin is clinically superior to clopidogrel–aspirin in this subgroup of patients with stroke is unclear.Aim: To describe the rationale and design considerations of the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE-2) trial.Design: CHANCE-2 is a randomised, double-blind, double-dummy, placebo-controlled, multicentre trial that compares two dual antiplatelet strategies for minor stroke or TIA patients who are CYP2C19 LOF allele carriers: ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily on days 2–90) or clopidogrel (300 mg loading dose on day 1 followed by 75 mg daily on days 2–90), plus open-label aspirin with a dose of 75–300 mg on day 1 followed by 75 mg daily on day 2–21. All will be followed for 1 year.Study outcomes: The primary efficacy outcome is any stroke (ischaemic or haemorrhagic) within 3 months and the primary safety outcome is any severe or moderate bleeding event within 3 months.Discussion: The CHANCE-2 trial will evaluate whether ticagrelor–aspirin is superior to clopidogrel–aspirin for minor stroke or TIA patients who are CYP2C19 LOF allele carriers

Association of CYP2C19 Loss-of-Function Metabolizer Status With Stroke Risk Among Chinese Patients Treated With Ticagrelor-Aspirin vs Clopidogrel-Aspirin: A Prespecified Secondary Analysis of a Randomized Clinical Trial.

Importance: The Clopidogrel With Aspirin in High-Risk Patients With Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial showed that ticagrelor-aspirin combination therapy reduced the risk of stroke compared with a clopidogrel-aspirin combination among carriers of CYP2C19 loss-of-function (LOF) alleles after a transient ischemic attack (TIA) or minor ischemic stroke. However, the association between the degree of CYP2C19 LOF and ideal treatment allocation remains unknown.Objective: To investigate whether the efficacy and safety of ticagrelor-aspirin vs clopidogrel-aspirin are consistent with the expected degree of CYP2C19 LOF after TIA or minor stroke.Design, Setting, and Participants: CHANCE-2 was a multicenter, double-blind, double-dummy, placebo-controlled randomized clinical trial. Patients were enrolled at 202 centers in China from September 23, 2019, through March 22, 2021. Patients with at least two *2 or *3 alleles (*2/*2, *2/*3, or *3/*3) according to point-of-care genotyping were classified as “poor metabolizers,” and those with one *2 or *3 allele (*1/*2 or *1/*3) were classified as “intermediate metabolizers.”Interventions: Patients were randomly assigned in a 1:1 ratio to receive ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily for days 2-90) or clopidogrel (300-mg loading dose on day 1 followed by 75 mg/d for days 2-90). All patients received aspirin (75- to 300-mg loading dose followed by 75 mg/d for 21 days).Main Outcomes and Measures: The primary efficacy outcome was a new ischemic or hemorrhagic stroke. The secondary efficacy outcome was a composite of new clinical vascular events and individual ischemic stroke events within 3 months. The primary safety outcome was severe or moderate bleeding. Analyses were performed according to the intention-to-treat principle.Results: Of the 6412 patients enrolled, the median age was 64.8 years (IQR, 57.0-71.4 years), and 4242 patients (66.2%) were men. Of the 6412 patients, 5001 (78.0%) were intermediate metabolizers, and 1411 (22.0%) were poor metabolizers. The primary outcome occurred less often with ticagrelor-aspirin vs clopidogrel-aspirin, irrespective of metabolizer status (6.0% [150 of 2486] vs 7.6% [191 of 2515]; hazard ratio [HR], 0.78 [95% CI, 0.63-0.97] among intermediate metabolizers and 5.7% [41 of 719] vs 7.5% [52 of 692]; HR, 0.77 [95% CI, 0.50-1.18] among poor metabolizers; P = .88 for interaction). Patients taking ticagrelor-aspirin had a higher risk of any bleeding event compared with those taking clopidogrel-aspirin, irrespective of metabolizer status: 5.4% (134 of 2486) vs 2.6% (66 of 2512) (HR, 2.14 [95% CI, 1.59-2.89]) among intermediate metabolizers and 5.0% (36 of 719) vs 2.0% (14 of 692) (HR, 2.99 [95% CI, 1.51-5.93]) among poor metabolizers (P = .66 for interaction).Conclusions and Relevance: This prespecified analysis of a randomized clinical trial found no difference in treatment effect between poor and intermediate CYP2C19 metabolizers. The relative clinical efficacy and safety of ticagrelor-aspirin vs clopidogrel-aspirin were consistent across CYP2C19 genotypes.Trial Registration: ClinicalTrials.gov Identifier: NCT0407873

Ticagrelor vs Clopidogrel in CYP2C19 loss-of-function carriers with Stroke or TIA

BACKGROUNDComparisons between ticagrelor- aspirin and clopidogrel-aspirin in CYP2C19 loss-of-function carriers have not been well studied for secondary stroke prevention.METHODSWe conducted a randomized, double-blind, placebo-controlled trial of 6,412 patients with a minor ischemic stroke or TIA who carried CYP2C19 LOF alleles determined by point-of-care testing. Patients were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio to receive ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or clopidogrel (300 mg loading dose on day 1 followed by 75 mg per day for days 2 through 90), plus aspirin (75-300 mg loading dose followed by 75 mg daily for 21 days). The primary efficacy outcome was stroke and the primary safety outcome was severe or moderate bleeding, both within 90 days. RESULTSStroke occurred within 90 days in 191 (6.0%) versus 243 (7.6%), respectively (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P=0.008). Moderate or severe bleeding occurred in 9 patients (0.3%) in the ticagrelor-aspirin group and in 11 patients (0.3%) in the clopidogrel-aspirin group; any bleeding event occurred in 170 patients (5.3%) vs 80 (2.5%), respectively. CONCLUSIONSAmong Chinese patients with minor ischemic stroke or TIA within 24 hours after symptoms onset who were carriers of CYP2C19 loss-of-function alleles, ticagrelor- aspirin was modestly better than clopidogrel-aspirin for reducing the risk of stroke but was associated with more total bleeding events at 90 days. (CHANCE-2 ClinicalTrials.gov number, NCT04078737.

Effects of a Corn Root Defense Substance on Western Corn Rootworm \u3ci\u3eDiabrotica virgifera virgifera\u3c/i\u3e LeConte Larvae

The objectives of this research were to evaluate the effects of hydroxamic acids, a group of corn root defense substances on western corn rootworm (Diabrotica virgifera virgifera LeConte) larvae and identify putative molecular mechanisms for hydroxamic acid detoxification. Corn line 428G carries a homozygous mutant bx1 gene, which makes it unable to synthesis hydroxamic acids. In contrast, H88 is the wild type parental line of 428G and is able to synthesize hydroxamic acids. Larvae were fed on 428G and H88 roots for 7 days for comparison. No significant difference was observed in growth, development, or survival rate. A RNA-Sequencing study was conducted to identify the differentially expressed genes that responded to dietary hydroxamic acids. A larval transcriptome sequence was assembled de novo from RNA-Sequencing data. Nine gene sequences were declared significantly differentially expressed. A putative cytochrome P450 gene was up regulated in the larvae feeding on hydroxamic acid-containing corn roots (H88). The results of this research suggested that hydroxamic acids do not have a significant inhibitory effect on western corn rootworm larvae. An inducible mechanism, mediated by cytochrome P450s, may be involved in hydroxamic acid detoxification. The results of this research advanced current understanding of western corn rootworm-corn interactions, and also provided a foundation for further study of the molecular mechanisms of hydroxamic acid detoxification by western corn rootworm. Advisor: Nicholas J. Mille