Search

In this study, numerous triaxial hydraulic fracturing experiments are performed in continental shale outcrop samples and artificial samples with similar properties to investigate the HF propagation behavior under single-cluster and multi-cluster fracturing treatments. The single-cluster fracturing experimental results show that the interlayer interface (IF) has a significant effect on the HF height containment, which tends to shear slip under conditions of low IF bonded strength, low vertical stress difference, low wellbore traversing layer strength and low q⋅μvalue (the product of injection rate and fracturing fluid viscosity), resulting in the arrest of HF by the IF, and the vertical propagation of HF is hindered. Seven types of HF geometries were observed under the interference of multiple IFs, which could be classified into three categories in the vertical plane based on degree of connection with IFs, namely, simple fracture, small-scale fishbone-like fracture, and large-scale fishbone-like fracture. The multi-cluster fracturing experimental results indicate that the vertical propagation law of HF under multi-cluster fracturing is similar to single-cluster fracturing. Under the conditions of small cluster spacing and large number of perforation clusters, it is difficult for each perforation cluster to initiate HF evenly, and the middle perforation cluster is more difficult than outers. In addition, injection-pressure curves in theory can provide some useful information for HF geometries identification. But it is difficult to judge whether the HFs initiate evenly and develop uniformly at multiple perforation clusters by observing the injection fracturing curves because the evolution law of the injection-pressure curves under the simultaneous propagation of multiple HFs and the propagation of a single HF are similar.

Genic male sterility (GMS) is one of the most important resources for exploiting heterosis in crop breeding, so that identifying genomic loci regulating GMS is desirable. However, many regulatory genes controlling GMS have not yet been characterized in maize, owing partly to a lack of genetic materials. We generated a recessive male-sterile maize mutant in the Jing 724 genetic background via ethyl methanesulfonate treatment, and found the male sterility to be due to a single gene mutation. Bulk-segregant RNA sequencing of three replicates indicated that one genomic region located at the end of chromosome 4 was associated with the observed mutant phenotype. Among genes with nonsynonymous mutations, Zm00001d053895(bHLH51) showed abolished expression in the sterile bulks and was annotated as a bHLH transcription factor orthologous to ArabidopsisAMS, suggesting an association with the male sterility of the mutant. Kompetitive Allele-Specific PCR assays further validated the exclusive correlation of male sterility with the single C-to-T mutation in the fifth exon. The new maize mutant and the potential SNP locus provide novel genetic material for investigating the molecular mechanism underlying tapetal development and may facilitate the improvement of hybrid production systems.

Dimethylarginine dimethylamino hydrolase-1 (DDAH-1) is an important regulator of nitric oxide (NO) metabolism that has been implicated in the pathogenesis of cardiovascular diseases. Nevertheless, its role in cerebral ischemia still needs to be elucidated. Herein, we examined the expression of DDAH-1 in the brain of rat by double-label immunofluorescence staining. DDAH-1 knock-out (DDAH-1−/−) and wild-type rats underwent middle cerebral artery occlusion/reperfusion (MCAO/R). After 24 h, neurological scores, TTC staining and TUNEL assay were used to evaluate neurological damages. 3 and 7-days infarct outcomes were also shown. Blood-brain-barrier (BBB) permeability was examined via Evans blue extravasation and tight junction (TJ) proteins expression and mRNA levels by western blot and RT-qPCR. The levels of plasma asymmetric dimethylarginine (ADMA), NO and ADMA in brain tissue were also assessed. In addition, supplementation of L-arginine to DDAH-1−/−rats was used to explore its role in regulating NO. DDAH-1 was abundantly distributed in cerebral cortex and basal nuclei, and mainly expressed in neurons and endothelial cells. DDAH-1−/−rats showed aggravated neurological damage and BBB disruption, including decrease of TJ proteins expression but indistinguishable mRNA levels after MCAO/R. DDAH-1 depletion and neurological damages were accompanied with increased ADMA levels and decreased NO concentrations. The supplementation with L-arginine partly restored the neurological damages and BBB disruption. To sum up, DDAH-1 revealed to have a protective role in ischemia stroke (IS) and IS-induced leakage of BBB via decreasing ADMA level and possibly via preventing TJ proteins degradation.

Background: Depression and anxiety after stroke are common conditions that are likely to be neglected. Abnormal red blood cell (RBC) indices may be associated with neuropsychiatric disorders. However, the association of RBC indices with post-stroke depression (PSD) and poststroke anxiety (PSA) has not been sufficiently investigated. Methods: We aimed to investigate the trajectory of post-stroke depression and anxiety in our follow- up stroke clinic at 1, 3, and 6 months, and the association of RBC indices with these. One hundred and sixty-two patients with a new diagnosis of ischemic stroke were followed up at 1, 3, and 6 months, and underwent Patient Health Questionnaire-9 (PHQ-9) and the general anxiety disorder 7-item (GAD-7) questionnaire for evaluation of depression and anxiety, respectively. First, we used Kaplan-Meier analysis to investigate the accumulated incidences of post-stroke depression and post-stroke anxiety. Next, to explore the association of RBC indices with psychiatric disorders after an ischemic stroke attack, we adjusted for demographic and vascular risk factors using multivariate Cox regression analysis. Results: Of the 162 patients with new-onset of ischemic stroke, we found the accumulated incidence rates of PSD (1.2%, 17.9%, and 35.8%) and PSA (1.2%, 13.6%, and 15.4%) at 1, 3, and 6 months, respectively. The incident PSD and PSA increased 3 months after a stroke attack. Multivariate Cox regression analysis indicated independent positive associations between PSD risk and higher mean corpuscular volume (MCV) (OR=1.42, 95% CI=1.16-1.76), older age (OR=2.63, 95% CI=1.16-5.93), and a negative relationship between male sex (OR=0.95, 95% CI=0.91-0.99) and PSA. Conclusion: The risks of PSD and PSA increased substantially 3 months beyond stroke onset. Of the RBC indices, higher MCV, showed an independent positive association with PSD.

Background: Intracranial Atherosclerotic Stenosis (ICAS) is an important risk factor for cognitive impairment. However, it is unclear whether patients with ICAS are more likely to develop cognitive impairment after an acute, non-disabling ischemic stroke (minor stroke). Objective: We aimed to investigate the association between ICAS and post-stroke cognitive impairment. Methods: In this cross-sectional study, patients with acute, non-disabling ischemic stroke underwent two cognitive tests and imaging evaluation for ICAS, within two weeks after the stroke. To determine the association between ICAS and post-stroke cognitive impairment, we performed a multivariate logistic regression analysis adjusted for several demographic and vascular risk factors. Results: Of the 164 patients with minor stroke in this study, 98 (59.76%) were diagnosed with poststroke cognitive impairment (Montreal Cognitive Assessment score<26). After adjusting for potential confounders, we found that patients with ICAS were more likely to develop cognitive impairment after an acute, non-disabling ischemic stroke, compared to patients without ICAS (Odds Ratio: 2.13; 95% Confidence Interval: 1.07-4.26), and underperformed in the tests of visuospatial and executive function. Conclusion: In this cross-sectional study of a population that has experienced a minor stroke, our findings demonstrated a positive association between ICAS and post-stroke cognitive impairment.

As a putative marker of cerebral small vessel disease, cerebral microbleeds (CMBs) have been associated with vascular cognitive impairment. Both iron accumulation and amyloid protein precursor (APP) dysregulation are recognized as pathological hallmarks underlying the progression of CMBs, but their cross-talk is not yet understood. In this study, we found a profound increase of amyloid formation with increasing FeCl3treatment, and a distinct change in APP metabolism and expression of iron homeostasis proteins (ferritin, Fpn1, iron regulatory protein) was observed at the 300 uM concentration of FeCl3. Further results revealed that extracellular iron accumulation might potentially induce binding of APP to BACE1 for amyloid formation and decrease the capability of APP/Fpn1 in mediating iron export. Our findings in this study, reflecting a probable relationship between iron dyshomeostasis and amyloid pathology, may help shed light on the underlying pathogenesis of CMBs in vascular cognitive impairment.

Mechanical thrombectomy (MT) is effective in managing patients with acute ischemic stroke (AIS) caused by large-vessel occlusions and allows for valuable histological analysis of thrombi. However, whether bridging therapy (pretreatment with intravenous thrombolysis before MT) provides additional benefits in patients with middle cerebral artery (MCA) occlusion remains unclear. Therefore, this study aimed to compare the effects of direct MT and bridging therapy, and to elucidate the correlation between thrombus composition and stroke subtypes. Seventy-three patients with acute ischemic stroke who received MT, were eligible for intravenous thrombolysis, and had MCA occlusion were included. We matched 21 direct MT patients with 21 bridging therapy patients using propensity score matching and compared their 3rd-month clinical outcomes. All MCA thrombi (n = 45) were histologically analyzed, and the red blood cell (RBC) and fibrin percentages were quantified. We compared the clot composition according to stroke etiology (large-artery atherosclerosis and cardioembolism) and intravenous thrombolysis application. The baseline characteristics showed no difference between groups except for a higher atrial fibrillation rate and NIHSS score on admission in the direct MT group. We performed a supportive analysis using propensity score matching but could not find any differences in the functional outcome, mortality, and intracerebral hemorrhage. In the histological clot analysis, the cardioembolic clots without intravenous thrombolysis pretreatment had higher RBC (P = 0.042) and lower fibrin (P = 0.042) percentages than the large-artery atherosclerosis thrombi. Similar findings were observed in the thrombi treated with recombinant tissue plasminogen activator (P = 0.012). In conclusion, there was no difference in the functional outcomes between the direct MT and bridging therapy groups. However, randomized trials are needed to elucidate the high ratio of cardioembolism subtype in our group of patients. The histological MCA thrombus composition differed between cardioembolism and large-artery atherosclerosis, and this finding provides valuable information on the underlying pathogenesis and thrombus origin.

Background: Cognitive impairment can occur after aneurysmal subarachnoid hemorrhage (aSAH) though it commonly tends to be neglected. Red blood cell (RBC) indices are associated with long-term functional outcomes, while it is unclear whether RBC indices could be a potential predictor of cognitive decline after aSAH. We aimed to investigate the association between RBC indices and post-aSAH cognitive impairment at 1 year. Methods: Patients with aSAH received neuropsychological test by the Montreal Cognitive Assessment (MoCA) and underwent serum and cerebrospinal fluid (CSF) samples test. To determine the association between RBC indices and cognitive impairment after acute aSAH, we adjusted for demographic and vascular risk factors using multivariate logistic regression analysis. Results: Of the 126 patients included in this study, 33% (42/126) of them were diagnosed with cognitive impairment (MoCA#156;26). After adjustment for potential confounders, increased mean corpuscular volume (MCV) (OR: 1.36, 95%CI: 1.19-1.55) and mean corpuscular hemoglobin (MCH) (OR: 1.61, 95%CI: 1.25-2.08), reflecting systemic iron status, are more likely to be associated with cognitive impairment after aSAH. Conclusion: In this aSAH population, our data shows the positive association between MCH and MCV and cognitive impairment at 1 year.

The high-nuclearity polyoxovanadate-based carboxylate derivative K6H[VV17VIV12(OH)4O60(OOC(CH2)4COO)8]·nH2O (1) has been successfully synthesized by conventional aqueous methods and structurally characterized. The [VV17VIV12(OH)4O60(OOC(CH2)4COO)8]7–polyanion is built up from three cages: one {VV17(OH)4O44} cage and two identical [(VIV3O6)2(OOC(CH2)4COO)4]8–cages. Of the three cages, the {VV17(OH)4O44} is a purely inorganic polyoxovanadate cluster, whereas each of the [(VIV3O6)2(OOC(CH2)4COO)4]8–cages is a vanadium-based organic–inorganic hybrid cluster framed via four adipate ligands linking simultaneously to two triangular {V3} units. The two [(VIV3O6)2(OOC(CH2)4COO)4]8–cages are covalently attached to the central {VV17(OH)4O44} cage via V–O–V bonds in a linear arrangement, resulting in a {V29}-based hybrid cluster skeleton. The catalytic properties of compound 1for the oxidation of sulfides by tert-butyl hydroperoxide were investigated, and the result indicates that 1exhibits excellent catalytic activity for the oxidation of sulfides under mild conditions.

Salt stress is a major abiotic factor limiting maize yield. To characterize the mechanism underlying maize salt tolerance, we compared the seedling root proteomes of salt-tolerant Jing724 and salt-sensitive D9H. The germination rate and growth parameter values (weight and length) were higher for Jing724 than for D9H under saline conditions. Using an iTRAQ-based method, we identified 513 differentially regulated proteins (DRPs), with 83 and 386 DRPs specific to Jing724 and D9H, respectively. In salt-stressed Jing724, the DRPs were primarily associated with the pentose phosphate pathway, glutathione metabolism, and nitrogen metabolism. Key DRPs, such as glucose-6-phosphate 1-dehydrogenase, NADPH-producing dehydrogenase, glutamate synthase, and glutamine synthetase, were identified based on pathway enrichment and protein–protein interaction analyses. Moreover, salt-responsive proteins in Jing724 seedlings were implicated in energy management, maintenance of redox homeostasis, detoxification of ammonia, regulation of osmotic homeostasis, stress defense and adaptation, biotic cross-tolerance, and regulation of gene expression. Quantitative analyses of superoxide dismutase activity, malondialdehyde content, relative electrolyte leakage, and proline content were consistent with the predicted changes based on DRP functions. Furthermore, changes in the abundance of eight representative DRPs were correlated with the corresponding mRNA levels. Our results may be useful for elucidating the molecular networks mediating salt tolerance.

Background: Identifying genotype-phenotype links and causative genes from quantitative trait loci (QTL) is challenging for complex agronomically important traits. To accelerate maize gene discovery and breeding, we present the Complete-diallel design plus Unbalanced Breeding-like Inter-Cross (CUBIC) population, consisting of 1404 individuals created by extensively inter-crossing 24 widely used Chinese maize founders. Results: Hundreds of QTL for 23 agronomic traits are uncovered with 14 million high-quality SNPs and a high-resolution identity-by-descent map, which account for an average of 75% of the heritability for each trait. We find epistasis contributes to phenotypic variance widely. Integrative cross-population analysis and cross-omics mapping allow effective and rapid discovery of underlying genes, validated here with a case study on leaf width. Conclusions: Through the integration of experimental genetics and genomics, our study provides useful resources and gene mining strategies to explore complex quantitative traits.