The role of leukocytes in acute ischemic stroke-related thrombosis: a notable but neglected topic.

Ischemic stroke is one of the most serious diseases today, and only a minority of patients are provided with effective clinical treatment. Importantly, leukocytes have gradually been discovered to play vital roles in stroke thrombosis, including promoting the activation of thrombin and the adhesion and aggregation of platelets. However, they have not received enough attention in the field of acute ischemic stroke. It is possible that we could not only prevent stroke-related thrombosis by inhibiting leukocyte activation, but also target leukocyte components to dissolve thrombi in the cerebral artery. In this review, we expound the mechanisms by which leukocytes are activated and participate in the formation of stroke thrombus, then describe the histopathology of leukocytes in thrombi of stroke patients and the influence of leukocyte composition on vascular recanalization effects and patient prognosis. Finally, we discuss the relevant antithrombotic strategies targeting leukocytes.

Full-Length Transcriptome Sequencing Reveals Alternative Splicing and lncRNA Regulation during Nodule Development in Glycine max.

Alternative splicing (AS) is a ubiquitous phenomenon among eukaryotic intron-containing genes, which greatly contributes to transcriptome and proteome diversity. Here we performed the isoform sequencing (Iso-Seq) of soybean underground tissues inoculated and uninoculated with Rhizobium and obtained 200,681 full-length transcripts covering 26,183 gene loci. It was found that 80.78% of the multi-exon loci produced more than one splicing variant. Comprehensive analysis of these identified 7874 differentially splicing events with highly diverse splicing patterns during nodule development, especially in defense and transport-related processes. We further profiled genes with differential isoform usage and revealed that 2008 multi-isoform loci underwent stage-specific or simultaneous major isoform switches after Rhizobium inoculation, indicating that AS is a vital way to regulate nodule development. Moreover, we took the lead in identifying 1563 high-confidence long non-coding RNAs (lncRNAs) in soybean, and 157 of them are differentially expressed during nodule development. Therefore, our study uncovers the landscape of AS during the soybean-Rhizobium interaction and provides systematic transcriptomic data for future study of multiple novel directions in soybean.

Neurologists' attitudes and options for anticoagulation therapy in central China.

AIMS: We aim to find out the factors affecting the use of anticoagulants and the intensity of their choices, and to establish a basis for improving neurologists' effective implementation of the guidelines. METHODS: A cross-sectional study is conducted in Hubei province in central China. Each neurologist completes a standard-structured anonymous questionnaire through face-to-face interviews. The problems include the attitude and options about anticoagulant therapy. RESULTS: A total of 611 neurologists from 38 hospitals respond to this survey. For the best treatment of atrial fibrillation, more than 80% of physicians choose anticoagulant therapy. For patients with atrial fibrillation and cerebral infarction, physicians think that Warfarin is the preferred drug as high as 93.8%. Among the anticoagulant drugs ever used by clinicians, the use rate of Warfarin is 93.8%, but the use rate of direct oral anticoagulants is insufficient. The use of direct oral anticoagulants is related to the educational level and the geographical location of the hospital. Bleeding risk is the first reason influencing clinicians' choice of Warfarin, accounts for 88.9%. 97.7% of the clinicians recommend patients with Warfarin to regularly monitor the INR, but the frequency of monitoring is inconsistent. Clinicians have a high willingness to learn about AF, but the proportion of hospitals that carry out appropriate training is low. CONCLUSIONS: There are still some gaps with the guidelines on the choice of anticoagulant drugs. Neurologists have positive attitude towards anticoagulant therapy and a strong willingness to learn, but the corresponding training is lacking. Continuous professional training is necessary.

RACK1 promotes miR-302b/c/d-3p expression and inhibits CCNO expression to induce cell apoptosis in cervical squamous cell carcinoma.

BACKGROUND: Cervical squamous cell carcinoma (CSCC) is one of the main causes of cancer-related deaths in women worldwide. The present study was conducted with the main objective of determining the potential role of receptor for activated protein kinase C1 (RACK1) in CSCC through regulation of microRNA (miR)-302b/c/d-3p and Cyclin O (CCNO). METHODS: The expression of RACK1, miR-302b/c/d-3p and CCNO in CSCC tissues and cells was measured by RT-qPCR and Western blot analysis. The interaction among RACK1, miR-302b/c/d-3p, and CCNO was determined by dual luciferase reporter assay. Subsequently, effects of RACK1, miR-302b/c/d-3p and CCNO on CSCC cell cycle entry, proliferation and apoptosis were investigated with the use of flow cytometry, EdU, and TUNEL assays. Furthermore, mouse xenograft model of CSCC cells was established to verify the function of RACK1 in vivo. RESULTS: RACK1 and miR-302b/c/d-3p were down-regulated and CCNO was overexpressed in CSCC. CCNO was identified as the target of miR-302b/c/d-3p. Importantly, overexpressed miR-302b-3p, miR-302c-3p or miR-302d-3p or RACK1 enhanced the apoptosis and suppressed the proliferation of CSCC cells in vitro, while inhibiting tumor growth in vivo by targeting CCNO. CONCLUSIONS: On all accounts, overexpressed RACK1 could dampen the progression of CSCC through miR-302b/c/d-3p-mediated CCNO inhibition.

Relationship between body composition indicators and risk of type 2 diabetes mellitus in Chinese adults.

BACKGROUND: Body composition is a crucial factor associated with the incidence of type 2 diabetes mellitus. However, no study on this relationship has been performed in the Chinese population. This study aimed to investigate the relationship between body composition indicators and risk of type 2 diabetes mellitus among Chinese adults undergoing medical examination. METHODS: Between January 2018 and July 2018, a retrospective cross-sectional study was performed on 3367 (2307 male and 1060 female) participants aged ≥18 years undergoing medical examination in Zhengzhou. Logistic regression analysis was performed to explore the relationship between body composition indicators and risk of type 2 diabetes mellitus. A receiver operating characteristic curve was used to calculate cutoff points and the predictive power of each indicator. RESULTS: Among the 3367 participants, 12.53% were diagnosed with type 2 diabetes mellitus. Multivariate logistic analysis indicated that male participants (odds ratio [OR] = 1.68, 95% confidence interval [CI]: 1.29-2.19), older participants (OR = 1.05, 95% CI: 1.04-1.06), participants with a waist-to-hip ratio above the reference value (OR = 1.56, 95% CI: 1.18-2.07), participants with body fat percentage above the reference value (OR = 1.62, 95% CI: 1.01-2.68), and participant with a large visceral fat area (OR = 1.01, 95% CI: 1.01-1.02) had a high risk of type 2 diabetes mellitus. Waist-to-hip ratio, body fat percentage, and visceral fat area were the best indicators of type 2 diabetes mellitus (P < 0.001) with cutoff values of 0.90, 25.02%, and 92.00 cm2, respectively. CONCLUSION: This study suggests a predictive relationship between type 2 diabetes mellitus and body composition indicators of waist-to-hip ratio, body fat percentage, and visceral fat area, which are valuable for screening diabetes and providing effective health education and behavioral intervention for high-risk populations.

Exosomal CagA derived from Helicobacter pylori-infected gastric epithelial cells induces macrophage foam cell formation and promotes atherosclerosis.

BACKGROUND: Seroepidemiological studies have highlighted a positive relation between CagA-positive Helicobacter pylori (H. pylori), atherosclerosis and related clinic events. However, this link has not been well validated. The present study was designed to explore the role of H. pylori PMSS1 (a CagA-positive strain that can translocate CagA into host cells) and exosomal CagA in the progression of atherosclerosis. METHODS: To evaluate whether H. pylori accelerates or even induces atherosclerosis, H. pylori-infected C57/BL6 mice and ApoE-/- mice were maintained under different dietary conditions. To identify the role of H. pylori-infected gastric epithelial cells-derived exosomes (Hp-GES-EVs) and exosomal CagA in atherosclerosis, ApoE-/- mice were given intravenous or intraperitoneal injections of saline, GES-EVs, Hp-GES-EVs, and recombinant CagA protein (rCagA). FINDINGS: CagA-positive H. pylori PMSS1 infection does not induce but promotes macrophage-derived foam cell formation and augments atherosclerotic plaque growth and instability in two animal models. Meanwhile, circulating Hp-GES-EVs are taken up in aortic plaque, and CagA is secreted in Hp-GES-EVs. Furthermore, the CagA-containing EVs and rCagA exacerbates macrophage-derived foam cell formation and lesion development in vitro and in vivo, recapitulating the pro-atherogenic effects of CagA-positive H. pylori. Mechanistically, CagA suppresses the transcription of cholesterol efflux transporters by downregulating the expression of transcriptional factors PPARγ and LXRα and thus enhances foam cell formation. INTERPRETATION: These results may provide new insights into the role of exosomal CagA in the pathogenesis of CagA-positive H. pylori infection-related atherosclerosis. It is suggested that preventing and eradicating CagA-positive H. pylori infection could reduce the incidence of atherosclerosis and related events.

A global coexpression network of soybean genes gives insights into the evolution of nodulation in nonlegumes and legumes.

A coexpression network is a powerful tool for revealing genes' relationship with many biological processes. Mass transcriptomic and genomic data from different plant species provide the foundation for understanding the evolution of nodulation across the Viridiplantae at a systematic level. We used weighted coexpression network analysis (WGCNA) to mine a nodule-related module (NRM) in Glycine max. Comparative genomic analysis of 78 green plant species revealed that NRM genes are recruited from different evolutionary nodes along with gene duplication events. A set of core coexpressed genes within legumes may play vital roles in regulating nodule environments essential for nitrogen fixation, including oxygen concentrations, sulfur transport, and iron homeostasis (such as GmCHY). The regulation of these genes occurred mainly at the transcription level, although some of them, such as sulfate transporters, may also undergo positive selection at protein level. We revealed that ancient orthologs and duplication events before the origin of legumes were preadapted for symbiosis. Conserved coregulated genes found within legumes paved the way for nodule formation and nitrogen fixation. These findings provide significant insights into the evolution of nodulation and indicate promising candidates for identifying other key components of legume nodulation and nitrogen fixation.

HAND2-AS1 inhibits invasion and metastasis of cervical cancer cells via microRNA-330-5p-mediated LDOC1.

BACKGROUND: Cervical cancer is a serious disease with complicated pathogenesis and thus there is an urgent need to find novel targets for the treatment. Recently, long non-coding RNAs (lncRNAs) have emerged as critical factors in tumorigenesis. In this study, we aimed to investigate the mechanism of HAND2 antisense RNA 1 (HAND2-AS1) on the invasion and metastasis of cervical cancer cells. METHODS: The expression patterns of HAND2-AS1, microRNA-330-5p (miR-330-5p) and leucine zipper down-regulated in cancer 1 (LDOC1) in cervical cancer were characterized by RT-qPCR and western blot analysis. Dual luciferase reporter assay and RIP were applied to verify relationship between HAND2-AS1, miR-330-5p and LDOC1. Fluorescence in situ hybridization (FISH) was used to detect the subcellular localization of HAND2-AS1. Besides, viability, invasion and migration ability of HeLa cells were investigated by cell counting kit-8 (CCK-8) and Transwell assays respectively. Hematoxylin-eosin staining was performed for lymph node metastasis detection. In addition, the tumor growth in nude mice was evaluated. RESULTS: Low expression of HAND2-AS1 and LDOC1, and high expression of miR-330-5p were detected in cervical cancer tissues and cells. It was found that binding of HAND2-AS1 to miR-330-5p results in upregulation of LDOC1 expression. Also, overexpressed HAND2-AS1 and LDOC1 or down-regulated miR-330-5p inhibited expression of proliferation-associated proteins Ki-67, PCNA, migration-associated proteins N-cad and invasion-related proteins MMP-2, MMP-9 as well as lymph node metastasis. Moreover, HAND2-AS1 inhibited tumor formation and lymph node metastasis by binding to miR-330-5p in vivo. CONCLUSION: HAND2-AS1 promotes LDOC1 expression by competitively binding to miR-330-5p and consequently inhibiting cervical cancer cell invasion and metastasis. This could facilitate development of therapeutic strategies against cervical cancer.

MicroRNA-130a regulates cerebral ischemia-induced blood-brain barrier permeability by targeting Homeobox A5.

Blood-brain barrier (BBB) disruption plays a critical role in brain injury induced by cerebral ischemia, and preserving BBB integrity during ischemia could alleviate cerebral injury. We examined the role of miR-130a in ischemic BBB disruption by using models of rat middle cerebral artery occlusion and cell oxygen-glucose deprivation. We found that ischemia significantly increased microRNA-130a (miR-130a) level and that miR-130a was predominantly from brain microvascular endothelial cells. Antagomir-130a, an antagonist of miR-130a, could attenuate brain edema, lower BBB permeability, reduce infarct volume, and improve neurologic function. MiR-130a overexpression induced by miR-130a mimic increased monolayer permeability, and intercellular inhibition of miR-130a by a miR-130a inhibitor suppressed oxygen-glucose deprivation-induced increase in monolayer permeability. Moreover, dual luciferase reporter system showed that Homeobox A5 was the direct target of miR-130a. MiR-130a, by inhibiting Homeobox A5 expression, could down-regulate occludin, thereby increasing BBB permeability. Our results suggested that miR-130a might be implicated in ischemia-induced BBB dysfunction and serve as a target for the treatment of ischemic stroke.-Wang, Y., Wang, M.-D., Xia, Y.-P., Gao, Y., Zhu, Y.-Y., Chen, S.-C., Mao, L., He, Q.-W., Yue, Z.-Y., Hu, B. MicroRNA-130a regulates cerebral ischemia-induced blood-brain barrier permeability by targeting Homeobox A5.

MicroRNA-23a-5p promotes atherosclerotic plaque progression and vulnerability by repressing ATP-binding cassette transporter A1/G1 in macrophages.

Disruption of carotid vulnerable atherosclerotic plaque is responsible for acute ischemic stroke (AIS) and the early detection and intervention approach are greatly limited. Undertaking a microarray of microRNAs (miRNAs) in the plasma of AIS patients with carotid vulnerable plaques, miR-23a-5p was markedly elevated and was positively correlated with the plaque progression and vulnerability. Correspondingly, we found that miR-23a-5p expression was significantly increased in both plasma and macrophages from atherosclerosis mice. Bioinformatics analysis and in vitro knockdown experiments identified that ATP-binding cassette transporter A1/G1 as a novel target of miR-23a-5p. Luciferase reporter assays showed that miR-23a-5p repressed the 3' untranslated regions (UTR) activity of ABCA1/G1. Moreover, functional analyses demonstrated that transfection of miR-23a-5p inhibitor enhanced cholesterol efflux and decreased foam cell formation through upregulating ABCA1/G1 expression levels. Furthermore, long term in vivo systemically delivered miR-23a-5p antagomir significantly increased ABCA1/G1 expression in the aorta of ApoE-/- mice. Importantly, the miR-23a-5p antagomir therapy significantly reduced atherosclerosis progression and promoted plaque stability. Our observations indicate that miR-23a-5p promotes macrophage-derived foam cell formation and might be a key regulator contributing to atherosclerotic plaque progression and vulnerability.

14-3-3ζ promotes esophageal squamous cell carcinoma invasion by repressing S1PR2 protein expression through NF-κB signaling.

14-3-3ζ is overexpressed in several cancers, including esophageal squamous cell carcinoma (ESCC), and plays an important role in tumorigenesis. However, the mechanisms underlying its tumorigenesis remain unclear. Here we report that 14-3-3ζ was upregulated in ESCC tumors, compared with adjacent normal tissues; 14-3-3ζ levels were positively correlated with ESCC lymph node metastasis and recurrence. Overexpression of 14-3-3ζ promoted the tumor growth and invasion of ESCC in vitro and in vivo, whereas depletion of 14-3-3ζ suppressed these effects. Moreover, 14-3-3ζ reduces expression of genes mediating S1P/S1PR2 signaling, and this effect is mediated through activation of NF- κ B. Taken together, 14-3-3ζ contributes to ESCC tumorigenesis and progression through repressing S1PR2 signaling and may act as a new therapeutic target for ESCC.

Identification of novel compound heterozygous SPG7 mutations-related hereditary spastic paraplegia in a Chinese family: a case report.

BACKGROUND: Autosomal recessive hereditary spastic paraplegias (ARHSPs) are a group of clinically and genetically heterogeneous neurodegenerative diseases with progressive spasticity and weakness in the lower limbs. Mutations in the Spastic Paraplegia gene 7 (SPG7) account for about 5-21% of ARHSP cases. However, in Asians, few reports about the mutations exist. In this study, we firstly report a novel finding from a Chinese family with compound heterozygous SPG7 mutations, in which three siblings were affected with a complicated form of ARHSP. CASE PRESENTATION: A 56-year-old man presented with progressive stiffness, weakness and ataxia in the lower limbs. Two sisters of him had similar symptoms and dysarthria. Brain magnetic resonance imaging (MRI) revealed cerebellar atrophy in each of the patients. Genetic analysis, which exerted a targeted next generation sequencing (NGS) panel covering 917 comprehensive ataxia genes to the proband, followed by Sanger sequencing of candidate genes in other eight family members, was used to find the etiology of the disease. Ultimately, we identified compound heterozygous SPG7 mutations with two mutations: (c.1150_1150-1insCTAC and c.2062C > T, p.Arg688Trp) and one single nucleotide polymorphism (c.2063G > A, p.Arg688Gln). CONCLUSIONS: The four bases insertion mutation (4bIM) was predicted to cause frameshift mutation or affect the splicing, and the last two variants were led to a stop codon mutation (p.Arg688Ter). As located in highly conserved positions and encoded paraplegin, the mutations were speculated to result in a truncated or defective protein and would be pathogenic factors of the disease. This paper proves to be the first case report of SPG7 mutation in ARHSP reported in Chinese population. Our findings widen the spectrum of SPG7 mutations of ARHSP and indicate that the SPG7 mutation is an important cause of adult-onset undiagnosed ataxia.

LncRNA TUG1 sponges microRNA-9 to promote neurons apoptosis by up-regulated Bcl2l11 under ischemia.

Emerging studies have illustrated that LncRNAs TUG1 play critical roles in multiple biologic processes. However, the LncRNA TUG1 expression and function in ischemic stroke have not been reported yet. In this study, we found that LncRNA TUG1 expression was significantly up-regulated in brain ischemic penumbra from rat middle carotid artery occlusion (MCAO) model, while similar results were also observed in cultured neurons under oxygen-glucose deprivation (OGD) insult. Knockdown of TUG1 decreased the ratio of apoptotic cells and promoted cells survival in vitro, which may be regulated by the elevated miRNA-9 expression and decreased Bcl2l11 protein. Furthermore, TUG1 could directly interact with miR-9 and down-regulating miR-9 could efficiently reverse the function of TUG1 on the Bcl2l11 expression. In summary, our result sheds light on the role of LncRNA TUG1 as a miRNA sponge for ischemic stroke, possibly providing a new therapeutic target in stroke.

Supra-Blan2 t score as a multisystem-based risk score to predict poor 3-month outcome in acute ischemic stroke patients with intravenous thrombolysis.

AIM: To develop and validate a novel weighted score integrating multisystem laboratory and clinical variables to predict poor 3-month outcome (mRS score of 3-6) in acute ischemic stroke (AIS) patients with intravenous thrombolysis (IVT) therapy. METHODS: We retrospectively analyzed data from Trial of Revascularization Treatment for Acute Ischemic Stroke study. The Supra-Blan2 t score was derived using the data on age, the National Institutes of Health Stroke Scale score, history of atrial fibrillation, blood sugar level, neutrophil count, direct bilirubin level, platelet-lymphocyte ratio, and TnI level in the derivation cohort of 433 patients, and validated in a cohort of 525 patients. Furthermore, we compared the performance of the Supra-Blan2 t score with DRAGON, TURN, and SPAN-100 scores. RESULTS: The discrimination capacity in the derivation and validation cohorts was good for poor 3-month outcome (the area under the curve was 0.821 and 0.843, respectively). The cumulative incidence of poor 3-month outcome significantly increased across risk categories in the derivation (low-risk, 9.2%; medium-risk, 17.4%; and high-risk, 58.8%) and validation cohorts (12.7%, 36.5%, and 73.6%, respectively). The performance of the Supra-Blan2 t score was similar to or superior to DRAGON, TURN, and SPAN-100 scores. CONCLUSION: The Supra-Blan2 t score, based on easily available multisystem laboratory and clinical variables, reliably predicted poor 3-month functional outcome in AIS patients treated with IVT therapy featuring good calibration and discrimination.

Association of white matter hyperintensities with long-term EGFR-TKI treatment and prediction of progression risk.

PURPOSE: The purpose of this study was to test the hypothesis that brain white matter hyperintensities (WMH) are more common in patients receiving epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and identify clinical risk factors associated with WMH. EXPERIMENTAL DESIGN: This multiple-center, prospective cohort study was conducted from March 2017 to July 2020. Two groups of patients with non-small cell lung cancer (NSCLC) who received or did not receive EGFR-TKI were included and followed up for more than 24 months. The progression of WMH was defined as an increase of ≥1 point on the Fazekas visual rating scale between the baseline and at the 2-year follow-up. A modified Poisson regression model was performed to evaluate risk factors on increased WMH load. RESULTS: Among 286 patients with NSCLC, 194 (68%) patients with NSCLC who received EGFR-TKI and 92 (32%) patients with NSCLC without EGFR-TKI treatment were analyzed. Modified Poisson regression analysis showed that EGFR-TKI treatment was independently associated with the WMH progression (EGFR-TKI: aRR 2.72, 95% confidence interval [CI] 1.46-5.06, p = .002). Interleukin (IL)-2, IL-4, and IL-10 were associated with increased WMH in the adjusted model (IL-2: aRR 1.55 [95% CI 1.06-2.25], p = .023; IL-4: aRR 1.66 [95% CI 1.13-2.43], p = .010; IL-10: aRR 1.48 [95% CI 1.06-2.06], p = .020). CONCLUSION: Patients with NSCLC who received EGFR-TKI may be at higher risk of developing WMH or worsening of WMH burden. The impact of increased WMH lesions in these patients is to be further assessed. IL-2, IL-4, and IL-10 may be used as potential biomarkers to monitor the risk of increased WMH burden.

CNS-LAND score: predicting early neurological deterioration after intravenous thrombolysis based on systemic responses and injury.

Importance: Early neurological deterioration (END) is a critical complication in acute ischemic stroke (AIS) patients receiving intravenous thrombolysis (IVT), with a need for reliable prediction tools to guide clinical interventions. Objective: This study aimed to develop and validate a rating scale, utilizing clinical variables and multisystem laboratory evaluation, to predict END after IVT. Design setting and participants: The Clinical Trial of Revascularization Treatment for Acute Ischemic Stroke (TRAIS) cohort enrolled consecutive AIS patients from 14 stroke centers in China (Jan 2018 to Jun 2022). Outcomes: END defined as NIHSS score increase >4 points or death within 24 h of stroke onset. Results: 1,213 patients (751 in the derivation cohort, 462 in the validation cohort) were included. The CNS-LAND score, a 9-point scale comprising seven variables (CK-MB, NIHSS score, systolic blood pressure, LDH, ALT, neutrophil, and D-dimer), demonstrated excellent differentiation of END (derivation cohort C statistic: 0.862; 95% CI: 0.796-0.928) and successful external validation (validation cohort C statistic: 0.851; 95% CI: 0.814-0.882). Risk stratification showed END risks of 2.1% vs. 29.5% (derivation cohort) and 2.6% vs. 31.2% (validation cohort) for scores 0-3 and 4-9, respectively. Conclusion: CNS-LAND score is a reliable predictor of END risk in AIS patients receiving IVT.

Predictive value of different bilirubin subtypes for clinical outcomes in patients with acute ischemic stroke receiving thrombolysis therapy.

AIMS: To explore the association of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) levels with, as well as the incremental predictive value of different bilirubin subtypes for, poor outcomes in acute ischemic stroke patients after thrombolysis. METHODS: We analyzed 588 individuals out of 718 AIS participants, and all patients were followed up at 3 months after thrombolysis. The primary outcome was 3-month death and major disability (modified Rankin Scale (mRS) score of 3-6). The secondary outcomes were 3-month mortality (mRS score of 6), moderate-severe cerebral edema, and symptomatic intracranial hemorrhage (sICH), respectively. RESULTS: Elevated DBIL pre-thrombolysis was associated with an increased risk of primary outcome (OR 3.228; 95% CI 1.595-6.535; p for trend = 0.014) after fully adjustment. Elevated TBIL pre-thrombolysis showed the similar results (OR 2.185; 95% CI 1.111-4.298; p for trend = 0.047), while IBIL pre-thrombolysis was not significantly associated with primary outcome (OR 1.895; 95% CI 0.974-3.687; p for trend = 0.090). Multivariable-adjusted spline regression model showed a positive linear dose-response relationship between DBIL pre-thrombolysis and risk of primary outcome (p for linearity = 0.004). Adding DBIL pre-thrombolysis into conventional model had greater incremental predictive value for primary outcome, with net reclassification improvement (NRI) 95% CI = 0.275 (0.084-0.466) and integrated discrimination improvement (IDI) 95% CI = 0.011 (0.001-0.024). Increased DBIL post-thrombolysis had an association with primary outcome (OR 2.416; 95%CI 1.184-4.930; p for trend = 0.039), and it also elevated the incremental predictive value for primary outcome, with NRI (95% CI) = 0.259 (0.066-0.453) and IDI (95% CI) = 0.025 (0.008-0.043). CONCLUSION: Increased DBIL pre-thrombolysis had a stronger association with, as well as greater incremental predictive value for, poor outcomes than TBIL and IBIL did in AIS patients after thrombolysis, which should be understood in the context of retrospective design. The effect of DBIL on targeted populations should be investigated in further researches.

The Role of Oxidative Stress in Acute Ischemic Stroke-Related Thrombosis.

Acute ischemic stroke is a serious life-threatening disease that affects almost 600 million people each year throughout the world with a mortality of more than 10%, while two-thirds of survivors remain disabled. However, the available treatments for ischemic stroke are still limited to thrombolysis and/or mechanical thrombectomy, and there is an urgent need for developing new therapeutic target. Recently, intravascular oxidative stress, derived from endothelial cells, platelets, and leukocytes, has been found to be tightly associated with stroke-related thrombosis. It not only promotes primary thrombus formation by damaging endothelial cells and platelets but also affects thrombus maturation and stability by modifying fibrin components. Thus, oxidative stress is expected to be a novel target for the prevention and treatment of ischemic stroke. In this review, we first discuss the mechanisms by which oxidative stress promotes stroke-related thrombosis, then summarize the oxidative stress biomarkers of stroke-related thrombosis, and finally put forward an antithrombotic therapy targeting oxidative stress in ischemic stroke.

Characterization of two constitutive promoters RPS28 and EIF1 for studying soybean growth, development, and symbiotic nodule development.

Native promoters that can drive high and stable transgene expression are important tools for modifying plant traits. Although several such promoters have been reported in soybean (Glycine max), few of them function at multiple growth and development stages and during nodule development. Here, we report that the promoters of 40S RIBOSOMAL PROTEIN SMALL SUBUNIT S28 (RPS28) and EUKARYOTIC TRANSLATION INITIATION FACTOR 1 (EIF1) are ideal for high expression of transgene. Through bioinformatic analysis, we determined that RPS28 and EIF1 were highly expressed during soybean growth and development, nodule development, and various biotic and abiotic stresses. Fusion of both RPS28 and EIF1 promoters, with or without their first intron, with the reporter gene ß-GLUCURONIDASE (uidA) in transgenic soybean, resulted in high GUS activity in seedlings, seeds, and nodules. Fluorimetric GUS assays showed that the RPS28 promoter and the EIF1 promoter yielded high expression, comparable to the soybean Ubiquitin (GmUbi) promoter. RPS28 and EIF1 promoters were also highly expressed in Arabidopsis thaliana and Nicotiana benthamiana. Our results indicate the potential of RPS28 and EIF1 promoters to facilitate future genetic engineering and breeding to improve the quality and yield of soybean, as well as in a wide variety of other plant species. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-022-00073-6.