Angiography-based hemodynamic features predict recurrent ischemic events after angioplasty and stenting of intracranial vertebrobasilar atherosclerotic stenosis.

OBJECTIVES: To assess the predictive value of hemodynamic features for stroke relapse in patients with intracranial vertebrobasilar atherosclerotic stenosis treated with percutaneous transluminal angioplasty and stenting (PTAS) using quantitative digital subtraction angiography (q-DSA). METHODS: In this retrospective longitudinal study, patients with intracranial vertebrobasilar atherosclerotic stenosis and who underwent PTAS treatment between January 2012 and May 2020 were enrolled. The q-DSA assessment was performed before and after PTAS. ROIs 1-4 were placed along the vertebral artery, proximal and distal basilar artery, and posterior cerebral artery; ROIs 5-8 were in 5 mm and 10 mm proximal and distal to the lesion, respectively. Relative time to peak (rTTP) was defined as the difference in TTP between ROIs. Cox regression analyses were performed to determine risk factors for recurrent stroke. RESULTS: A total of 137 patients (mean age, 62 years ± 10 [standard deviation], 83.2% males) were included, and 26 (19.0%) patients had stroke relapse during follow-up (median time of 42.6 months [interquartile range, 19.7-60.7]). Preprocedural rTTP4-1 (adjusted hazard ratio (HR) = 2.270; 95% CI 1.371-3.758; p = 0.001) and preprocedural rTTP8-5 (adjusted HR = 0.240; 95% CI 0.088-0.658; p = 0.006) were independently associated with the recurrent stroke. These hemodynamic parameters provided an incremental prognostic value for stroke relapse (AUC, 0.817 [0.704-0.931]; the net reclassification index, 0.431 [0.057-0.625]; and the integrated discrimination index, 0.140 [0.035-0.292]). CONCLUSIONS: In patients with intracranial vertebrobasilar atherosclerosis treated with PTAS, preprocedural prolonged TTP of the target vessel and shortened trans-stenotic TTP difference were associated with stroke relapse. Q-DSA-defined hemodynamic parameters provided incremental predictive value over conventional parameters for stroke recurrence. CLINICAL RELEVANCE STATEMENT: Quantitative DSA analysis enables intuitive observation and semi-quantitative evaluation of peri-therapeutic cerebral blood flow. More importantly, quantitative DSA-defined hemodynamic parameters have the potential for risk stratification of patients with intracranial atherosclerotic stenosis. KEY POINTS: Semi-quantitative angiography-based parameters can reflect pre- and postprocedural subtle changes in blood flow in patients with intracranial atherosclerotic stenosis. Although angioplasty procedures can significantly improve blood flow status, patients with more restricted baseline blood flow still show a higher risk of stroke recurrence. Angiography-based hemodynamic features possess prognostic value and can serve as clinical markers to assess stroke risk of patients with intracranial atherosclerotic stenosis.

Elucidating the association of obstructive sleep apnea with brain structure and cognitive performance.

BACKGROUND: Obstructive sleep apnea (OSA) is a pervasive, chronic sleep-related respiratory condition that causes brain structural alterations and cognitive impairments. However, the causal association of OSA with brain morphology and cognitive performance has not been determined. METHODS: We conducted a two-sample bidirectional Mendelian randomization (MR) analysis to investigate the causal relationship between OSA and a range of neurocognitive characteristics, including brain cortical structure, brain subcortical structure, brain structural change across the lifespan, and cognitive performance. Summary-level GWAS data for OSA from the FinnGen consortium was used to identify genetically predicted OSA. Data regarding neurocognitive characteristics were obtained from published meta-analysis studies. Linkage disequilibrium score regression analysis was employed to reveal genetic correlations between OSA and related traits. RESULTS: Our MR study provided evidence that OSA was found to significantly increase the volume of the hippocampus (IVW ß (95% CI) = 158.997 (76.768 to 241.227), P = 1.51e-04), with no heterogeneity and pleiotropy detected. Nominally causal effects of OSA on brain structures, such as the thickness of the temporal pole with or without global weighted, amygdala structure change, and cerebellum white matter change covering lifespan, were observed. Bidirectional causal links were also detected between brain cortical structure, brain subcortical, cognitive performance, and OSA risk. LDSC regression analysis showed no significant correlation between OSA and hippocampus volume. CONCLUSIONS: Overall, we observed a positive association between genetically predicted OSA and hippocampus volume. These findings may provide new insights into the bidirectional links between OSA and neurocognitive features, including brain morphology and cognitive performance.

Impact of miR-200b and miR-495 variants on the risk of large-artery atherosclerosis stroke.

Single-nucleotide polymorphisms (SNPs) of microRNAs (miRNAs) may alter miRNA transcription, maturation and target specificity, thus affecting stroke susceptibility. We aimed to investigate whether miR-200b and miR-495 SNPs may be associated with ischemic stroke (IS) risk and further explore underlying mechanisms including related genes and pathways. MiR-200b rs7549819 and miR-495 rs2281611 polymorphisms were genotyped among 712 large-artery atherosclerosis (LAA) stroke patients and 1,076 controls in a case-control study. Bioinformatic analyses were performed to explore potential association of miR-200b/495 with IS and to examine the effects of these two SNPs on miR-200b/495. Furthermore, we evaluated the association between these two SNPs and stroke using the public GWAS datasets. In our case-control study, rs7549819 was significantly associated with a decreased risk of LAA stroke (OR = 0.73, 95% CI = 0.58-0.92; p = 0.007), while rs2281611 had no significant association with LAA stroke risk. These results were consistent with the findings in East Asians from the GIGASTROKE study. Combined effects analysis revealed that individuals with 2-4 protective alleles (miR-200bC and miR-495 T) exhibited lower risk of LAA stroke than those with 0-1 variants (OR = 0.76, 95% CI = 0.61-0.96; p = 0.021). Bioinformatic analyses showed that miR-200b and miR-495 were significantly associated with genes and pathways related to IS pathogenesis, and rs7549819 and rs2281611 markedly influenced miRNA expression and structure. MiR-200b rs7549819 polymorphism and the combined genotypes of miR-200b rs7549819 and miR-495 rs2281611 polymorphisms were associated with decreased risk of LAA stroke in Chinese population.

The mediating role of atrial fibrillation in causal associations between risk factors and stroke: a Mendelian randomization study.

OBJECTIVES: Atrial fibrillation (AF) contributes to stroke development and progression. We aimed to quantify the mediating role of AF in the causal associations between a wide range of risk factors and stroke via a Mendelian randomization (MR) framework. METHODS: We assessed the associations of 108 traits with stroke and its subtypes in a 2-sample univariable MR approach, then conducted a bidirectional MR analysis between these 108 traits and AF to evaluate the presence and direction of their causal associations. Finally, to further investigate the extent to which AF mediated the effects of eligible traits on stroke, we applied multivariable and 2-step MR techniques in a mediation analysis where outcomes were restricted to stroke types causally affected by AF (any stroke [AS], any ischemic stroke [AIS], and cardioembolic stroke [CES]). RESULTS: Among 108 traits, 42 were putatively causal for at least 1 stroke type; of these 42 traits, 20 that had no bidirectional relationship with AF were retained. Finally, 33 associations of 15 eligible traits were examined in the mediation analysis. The mediation analyses for AS, AIS, and CES each included 11 eligible traits. After AF adjustment, the direct effects of all traits on CES were attenuated to null (all p>0.05), while the associations with AS and AIS persisted for most traits (AF-mediated proportion: from 6.6% [95% confidence interval, 2.7 to 0.6] to 52.0% [95% confidence interval, 39.8 to 64.3]). CONCLUSIONS: The causal associations between all eligible traits and CES were largely mediated through AF, while most traits affected AS and AIS independently of AF.

Improving radish phosphorus utilization efficiency and inhibiting Cd and Pb uptake by using heavy metal-immobilizing and phosphate-solubilizing bacteria.

Phosphate-solubilizing bacteria play a key role in increasing plant growth as potential suppliers of soluble phosphorus and have great potential for the remediation of heavy metal-polluted soils. However, the soil and microbiological mechanisms by which phosphate-solubilizing bacteria prevent heavy metal absorption in radish have not been adequately studied. Here, the mechanisms of phosphorus solubilization, Cd and Pb immobilization, and the inhibition of heavy metal absorption by phosphate-solubilizing bacteria were studied in radish through solution adsorption and pot experiments. Two phosphate-solubilizing bacteria with high Cd and Pb removal rates (46.9-97.12 %), Klebsiella sp. M2 and Kluyvera sp. M8, were isolated. The soluble phosphorus content released by strains M2 and M8 was 265-277 mg L-1, achieved by secreting oxalic acid, ascorbic acid, citric acid, and succinic acid in an inorganic phosphorus medium containing 3 mg L-1 Cd and 5 mg L-1 Pb. Furthermore, these two functional strains induced the formation of Pb2(PO4)2, Cd(PO3)2, Fe2Pb3(PO4)2, CdS, and PbS precipitates that immobilized Cd and Pb in the solution. In general, strains M2 and M8 inhibited the absorption of Cd and Pb by radish by the following mechanisms: i) bacterial cell wall adsorption, ii) induction of Pb2(PO4)2, Cd(PO3)2, Fe2Pb3(PO4)2, CdS, and PbS precipitation in the solution/soil, iii) increases in the Ca2P and FeP contents in the radish rhizosphere, and iv) the promotion of bacterial community enrichment toward phosphorus-solubilizing and plant growth-promoting properties (Ramlibacter, Enterobacter, Bacillus, Gemmatimonas, and Lysinibacillusin) in the radish rhizosphere. These results provide bacterial resources and technical approaches to heavy metal pollution amelioration and efficient phosphorus fertilizer use in farmland.

[Polyamine-producing Bacteria Regulated the Community Structure of Rhizosphere Bacteria and Reduced the Absorption of Cd in Wheat].

Some functional microorganisms in the soil immobilize heavy metals by adsorption and precipitation, prevent the absorption of heavy metals by crops, and play an important role in the passivation and remediation of medium and mild heavy metal-contaminated soil. A pot experiment was conducted to study the effects of the exogenous polyamine-producing bacterium Bacillus sp. N3 on Cd uptake and the bacterial community composition and function in the rhizosphere soil. The results showed that strain N3 significantly reduced the contents of Cd (64.7%) in wheat grain and DTPA-Cd (50.1%) in rhizosphere soil and increased the pH (from 6.84 to 6.97) and polyamine content. High-throughput sequencing results showed that inoculation of strain N3 reduced the diversity of the bacterial community; however, it increased the relative abundances of ß-Proteobacteria, Bacteroidetes, and Firmicutes in wheat rhizosphere soil. Meanwhile, strain N3 also increased the relative abundances of heavy metal-immobilizing bacteria and plant growth-promoting bacteria (Bacillus, Arthrobacter, Brevundimonas, Ensifer, Pedobacter, Rhizobium, Pseudomonas, Enterobacter, and Serratia) in wheat rhizosphere soil. The PICRUSt function prediction showed that strain N3 increased the copy number of genes involved in antioxidant capacity, hormone synthesis, and sulfur metabolism in wheat rhizosphere soil. These results indicated that the polyamine-producing bacteria N3 reduced the DTPA-Cd content by increasing the pH; the polyamine contents; the abundances of bacteria with heavy metal-immobilizing or plant growth-promoting traits; and the metabolic pathway involved in antioxidant capacity, hormone synthesis, and sulfur metabolism in wheat rhizosphere soil, thus inhibiting the absorption of Cd by wheat. The results provide theoretical basis and technical support for restoring farmland with excessive heavy metals and ensuring the safe production of wheat.

Mechanisms of Enterobacter bugandensis TJ6 immobilization of heavy metals and inhibition of Cd and Pb uptake by wheat based on metabolomics and proteomics.

Microbial passivation remediation of heavy metal-contaminated farmland has attracted increasing attention. However, the molecular mechanism by which heavy metal-immobilizing bacteria inhibit the uptake of Cd and Pb by wheat is not clear. Herein, a heavy metal-immobilizing bacterium, Enterobacter bugandensis TJ6, was used to reveal its immobilization mechanisms of Cd and Pb and inhibition of Cd and Pb uptake by wheat using metabolomics and proteomics. Compared with the control, strain TJ6 significantly reduced (44.7%-56.6%) the Cd and Pb contents of wheat roots and leaves. Strain TJ6 reduced the Cd and Pb concentrations by adsorption, intracellular accumulation, and bioprecipitation in solution. Untargeted metabolomics showed that strain TJ6 produced indole-3-acetic acid (IAA), betaine, and arginine under Cd and Pb stress, significantly improving the resistance of strain TJ6 and wheat to Cd and Pb. Label-free proteomics showed that 143 proteins were upregulated and 61 proteins were downregulated in wheat roots in the presence of strain TJ6. The GO items of the differentially expressed proteins (DEPs) involved in protein-DNA complexes, DNA packaging complexes, and peroxidase activity were enriched. In addition, the ability of wheat roots to synthesize abscisic acid and jasmonic acid was improved. In conclusion, strain TJ6 reduced Cd and Pb uptake in wheat through its own adsorption of Cd and Pb and regulation of wheat root DNA repair ability, plant hormone levels, and antioxidant activities. These results provide new insights and a theoretical basis for the application of heavy metal-immobilizing bacteria in safe wheat production.