Plasma Exosomal CXCL7 is a Potential Biomarker for Lung Adenocarcinoma.

BACKGROUND: Lung cancer is a leading cause of cancer-related death, with lung adenocarcinoma (LUAD) representing the most common subtype. Recently, exosome-based biomarkers have provided new diagnostic approaches for malignancies. METHODS: The differential expression profile of plasma exosomal mRNA was established by high-throughput sequencing, and the expression and diagnostic value of plasma exosomal CXCL7 mRNA and protein in LUAD were studied to evaluate their diagnostic value as tumor biomarkers. RESULTS: The expression of plasma exosomal CXCL7 mRNA in patients with LUAD was significantly increased (p < 0.01), which had no significant correlation with age, gender, and stage. ROC was used to evaluate the diagnostic value of plasma exosomal CXCL7 mRNA in LUAD patients with AUC = 0.7171. Further analysis signified that the CXCL7 protein of plasma exosomes in LUAD patients was overexpressed, and it was positively correlated with TNM stage and age. The diagnostic value of plasma exosomal CXCL7 in LUAD is better than serum CEA, with an AUC of 0.785, which has higher sensitivity and specificity. CONCLUSIONS: This research suggests that plasma exosomal CXCL7 may become an effective biomarker for early diagnosis of LUAD.

Benefit of endovascular treatment for primary versus secondary medium vessel occlusion: A multi-center experience.

AIMS: This study aimed to compare the clinical outcomes and safety of endovascular treatment (EVT) in patients with primary versus secondary medium vessel occlusion (MeVO). METHODS: From the endovascular treatment for acute ischemic stroke in the China registry, we collected consecutive patients with MeVO who received EVT. The primary endpoint was a good outcome, defined as a modified Rankin Scale (mRS) 0 to 2 at 90 days. RESULTS: 154 patients were enrolled in the final analysis, including 74 primary MeVO and 80 secondary MeVO. A good outcome at 90 days was achieved in 42 (56.8%) patients with primary MeVO and 33 (41.3%) patients with secondary MeVO. There was a higher probability of good outcomes in patients with the primary vs secondary MeVO (adjusted odds ratio, 2.16; 95% confidence interval, 1.04 to 4.46; p = 0.04). There were no significant differences in secondary and safety outcomes between MeVO groups. In the multivariable analysis, baseline ASPECTS (p = 0.001), final modified thrombolysis in cerebral infarction score (p = 0.01), and any ICH (p = 0.03) were significantly associated with good outcomes in primary MeVO patients, while baseline National Institutes of Health Stroke Scale (p = 0.002), groin puncture to recanalization time (p = 0.02), and early neurological improvement (p < 0.001) were factors associated with good outcome in secondary MeVO patients. CONCLUSION: In MeVO patients who received EVT, there was a higher likelihood of poor outcomes in patients with secondary versus primary MeVO.

Systolic blood pressure and early neurological deterioration in minor stroke: A post hoc analysis of ARAMIS trial.

BACKGROUND: Systolic blood pressure (SBP) was a predictor of early neurological deterioration (END) in stroke. We performed a secondary analysis of ARAMIS trial to investigate whether baseline SBP affects the effect of dual antiplatelet versus intravenous alteplase on END. METHODS: This post hoc analysis included patients in the as-treated analysis set. According to SBP at admission, patients were divided into SBP ≥140 mmHg and SBP <140 mmHg subgroups. In each subgroup, patients were further classified into dual antiplatelet and intravenous alteplase treatment groups based on study drug actually received. Primary outcome was END, defined as an increase of ≥2 in the NIHSS score from baseline within 24 h. We investigated effect of dual antiplatelet vs intravenous alteplase on END in SBP subgroups and their interaction effect with subgroups. RESULTS: A total of 723 patients from as-treated analysis set were included: 344 were assigned into dual antiplatelet group and 379 into intravenous alteplase group. For primary outcome, there was more treatment effect of dual antiplatelet in SBP ≥140 mmHg subgroup (adjusted RD, -5.2%; 95% CI, -8.2% to -2.3%; p < 0.001) and no effect in SBP <140 mmHg subgroup (adjusted RD, -0.1%; 95% CI, -8.0% to 7.7%; p = 0.97), but no significant interaction between subgroups was found (adjusted p = 0.20). CONCLUSIONS: Among patients with minor nondisabling acute ischemic stroke, dual antiplatelet may be better than alteplase with respect to preventing END within 24 h when baseline SBP ≥140 mmHg.

Lipidomics-based insights into the physiological mechanism of wheat in response to heat stress.

Lipids are the main components of plant cell biofilms and play a crucial role in plant growth, Understanding the modulation in lipid profiles under heat stress can contribute to understanding the heat tolerance mechanisms in wheat leaves. In the current study, two wheat cultivars with different heat tolerance levels were treated with optimum temperature (OT) and high temperature (HT) at the flowering stage, and the antioxidant enzyme activity in the leaves and the grain yield were determined. Further, lipidomics was studied to determine the changes in lipid composition in the leaves. The heat-tolerant cultivar ZM7698 exhibited higher antioxidant enzyme activity and lower malondialdehyde and H2O2 contents. High-temperature stress led to the remodeling of lipid profile in the two cultivars. The relative proportion of digalactosyl diacylglycerol (DGDG) and phosphatidylinositol (PI) components increased in the heat-tolerant cultivar under high-temperature stress, while it was decreased in the heat-sensitive cultivar. The lipid unsaturation levels of sulfoquinovosyl diacylglycerol (SQDG), monogalactosyl monoacylglycerol (MGMG), and phosphatidic acid (PA) decreased significantly in the heat-tolerant cultivar under high-temperature stress. The increase in unsaturation of monogalactosyl diacylglycerol (MGDG) and phosphatidylethanolamine (PE) in the heat-tolerant cultivar under high-temperature stress was lower than in the heat-sensitive cultivar. In addition, a high sitosterol/stigmasterol (SiE/StE) ratio was observed in heat-tolerant cultivar under high-temperature stress. Taken together, these results revealed that a heat-tolerant cultivar could enhance its ability to resist heat stress by modulating the composition and ratio of the lipid components and decreasing lipid unsaturation levels in wheat.

Rescue thrombolysis for medium vessel occlusion (RESCUE-TNK): Rationale and design of a phase 2 randomized trial.

Background: The best reperfusion strategy for medium-sized vessel occlusion (MeVO) is not well established. Given the proven treatment effect of intra-arterial thrombolysis in patients with large vessel occlusion (LVO), we hypothesized that intra-arterial tenecteplase (TNK) could increase the recanalization rate of MeVO and thus improve clinical outcome. Aims: To explore the safety and efficacy of intra-arterial TNK in patients with MeVO. Sample size estimates: A maximum of 80 patients are required to test the superiority hypothesis, using power = 80% and α = 0.025 to conduct the one-sided test. Design: Rescue treatment for mEdium veSsel oCclUsion by intra-artErial TNK (RESCUE-TNK) is a pilot, randomized, open-label, blinded end point, and multicenter trial. Eligible patients including primary MeVO as detected by the first DSA examination or secondary MeVO after endovascular treatment (EVT) for LVO will be assigned into the experimental group and control group as a ratio of 1:1. The experimental group will be treated with intra-arterial TNK (0.2-0.3 mg/min, for 20-30 min) via a microcatheter placed proximal to the site of occlusion, and the control group will be treated with routine therapy. Both groups of patients will be given standard stroke care based on the guidelines. Outcome: The primary efficacy end point is successful recanalization of MeVO, defined as the expanded treatment in cerebral ischemia (eTICI) score 2b67-3 after the procedure, while the primary safety end point is symptomatic intracranial hemorrhage (sICH), defined as National Institutes of Health Stroke Scale score increase ≥4 caused by intracranial hemorrhage within 24 (-6/+24) hours after randomization. Conclusion: The results of RESCUE-TNK will provide evidence for the efficacy and safety of intra-arterial TNK in the recanalization of patients with MeVO.

Dynamic Metabolomics and Transcriptomics Analyses for Characterization of Phenolic Compounds and Their Biosynthetic Characteristics in Wheat Grain.

Phenolic compounds are important bioactive phytochemicals with potential health benefits. In this study, integrated metabolomics and transcriptomics analysis was used to analyze the metabolites and differentially expressed genes in grains of two wheat cultivars (HPm512 with high antioxidant activity, and ZM22 with low antioxidant activity) during grain development. A total of 188 differentially expressed phenolic components, including 82 phenolic acids, 81 flavonoids, 10 lignans, and 15 other phenolics, were identified in the developing wheat grains, of which apigenin glycosides were identified as the primary flavonoid component. The relative abundance of identified phenolics showed a decreasing trend with grain development. Additionally, 51 differentially expressed phenolic components were identified between HPm512 and ZM22, of which 41 components, including 23 flavonoids, were up-regulated in HPm512. In developing grain, most of the identified differentially expressed genes involved in phenolic accumulation followed a similar trend. Integrated metabolomics and transcriptomics analysis revealed that certain genes encoding structural proteins, glycosyltransferase, and transcription factors were closely related to metabolite accumulation. The relatively higher accumulation of phenolics in HPm512 could be due to up-regulated structural and regulatory genes. A sketch map was drawn to depict the synthetic pathway of identified phenolics and their corresponding genes. This study enhanced the current understanding of the accumulation of phenolics in wheat grains. Besides, active components and their related genes were also identified, providing crucial information for the improvement of wheat's nutritional quality.

Salt modulates gravity signaling pathway to regulate growth direction of primary roots in Arabidopsis.

Plant root architecture is highly plastic during development and can adapt to many environmental stresses. The proper distribution of roots within the soil under various conditions such as salinity, water deficit, and nutrient deficiency greatly affects plant survival. Salinity profoundly affects the root system architecture of Arabidopsis (Arabidopsis thaliana). However, despite the inhibitory effects of salinity on root length and the number of roots, very little is known concerning influence of salinity on root growth direction and the underlying mechanisms. Here we show that salt modulates root growth direction by reducing the gravity response. Exposure to salt stress causes rapid degradation of amyloplasts in root columella cells of Arabidopsis. The altered root growth direction in response to salt was found to be correlated with PIN-FORMED2 (PIN2) messenger RNA abundance and expression and localization of the protein. Furthermore, responsiveness to gravity of salt overly sensitive (sos) mutants is substantially reduced, indicating that salt-induced altered gravitropism of root growth is mediated by ion disequilibrium. Mutation of SOS genes also leads to reduced amyloplast degradation in root tip columella cells and the defects in PIN2 gene expression in response to salt stress. These results indicate that the SOS pathway may mediate the decrease of PIN2 messenger RNA in salinity-induced modification of gravitropic response in Arabidopsis roots. Our findings provide new insights into the development of a root system necessary for plant adaptation to high salinity and implicate an important role of the SOS signaling pathway in this process.

Arabidopsis EIN2 modulates stress response through abscisic acid response pathway.

The nuclear protein ETHYLENE INSENSITIVE2 (EIN2) is a central component of the ethylene signal transduction pathway in plants, and plays an important role in mediating cross-links between several hormone response pathways, including abscisic acid (ABA). ABA mediates stress responses in plants, but there is no report on the role of EIN2 on plant response to salt and osmotic stresses. Here, we show that EIN2 gene regulates plant response to osmotic and salt stress through an ABA-dependent pathway in Arabidopsis. The expression of the EIN2 gene is down-regulated by salt and osmotic stress. An Arabidopsis EIN2 null mutant was supersensitive to both salt and osmotic stress conditions. Disruption of EIN2 specifically altered the expression pattern of stress marker gene RD29B in response to the stresses, but not the stress- or ABA-responsive genes RD29A and RD22, suggesting EIN2 modulates plant stress responses through the RD29B branch of the ABA response. Furthermore, disruption of EIN2 caused substantial increase in ABA. Lastly, our data showed that mutations of other key genes in ethylene pathway also had altered sensitivity to abiotic stresses, indicating that the intact ethylene may involve in the stress response. Taken together, the results identified EIN2 as a cross-link node in ethylene, ABA and stress signaling pathways, and EIN2 is necessary to induce developmental arrest during seed germination, and seedling establishment, as well as subsequent vegetative growth, thereby allowing the survival and growth of plants under the adverse environmental conditions.