Association and temporal sequence of pneumonia and gastrointestinal bleeding after acute ischemic stroke.

BACKGROUND: Stroke-associated pneumonia (SAP) and gastrointestinal bleeding (GIB) are common medical complications after stroke. The previous study suggested a strong association between SAP and GIB after stroke. However, little is known about the time sequence of SAP and GIB. In the present study, we aimed to verify the association and clarify the temporal sequence of SAP and GIB after ischemic stroke. METHODS: Patients with ischemic stroke from in-hospital Medical Complication after Acute Stroke study were analyzed. Data on occurrences of SAP and GIB during hospitalization and the intervals from stroke onset to diagnosis of SAP and GIB were collected. Multiple logistic regression was used to evaluate the association between SAP and GIB. Kruskal-Wallis test was used to compare the time intervals from stroke onset to diagnosis of SAP and GIB. RESULTS: A total of 1129 patients with ischemic stroke were included. The median length of hospitalization was 14 days. Overall, 86 patients (7.6%; 95% CI, 6.1-9.2%) developed SAP and 47 patients (4.3%; 95% CI, 3.0-5.3%) developed GIB during hospitalization. After adjusting potential confounders, SAP was significantly associated with the development of GIB after ischemic stroke (OR = 5.13; 95% CI, 2.02-13.00; P < 0.001). The median time from stroke onset to diagnosis of SAP was shorter than that of GIB after ischemic stroke (4 days vs. 5 days; P = 0.039). CONCLUSIONS: SAP was associated with GIB after ischemic stroke, and the onset time of SAP was earlier than that of GIB. It is imperative to take precautions to prevent GIB in stroke patients with SAP.

Hydrazone bond-oriented molecularly imprinted nanocomposites for the selective separation of protein via the well-defined recognition sites.

The development of hydrazone bond-oriented epitope imprinting strategy is reported to synthesize the polymeric binders for the selective recognition of a protein-ß2-microglobulin through either its N- or C-terminal epitope. The dynamic reversibility of hydrazone bond facilitated not only the oriented assembly of the template peptide hydrazides onto the substrate but also the efficient removal of them from the imprinted cavities. The well-defined surface imprinted layer was successfully constructed through the precise control over the polymerization of silicate esters. Binding performance of the C-terminal peptide imprinted nanocomposite was significantly improved after tuning the non-covalent interactions using the sequence-matching aromatic co-monomers. The dissociation constant (Kd) between the optimized nanocomposite and epitope peptide was 0.5 µmol L-1. The nanomaterial was utilized for the selective extraction and determination of ß2-microglobulin from human urine by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and HPLC-UV with satisfied recoveries of 93.1-112.3% in a concentration range 1.0-50.0 µg⋅mL-1.

Electrochemically induced synthesis of quinazolinones via cathode hydration of o-aminobenzonitriles in aqueous solutions.

An efficient and practical electrochemically catalyzed transition metal-free process for the synthesis of substituted quinazolinones from simple and readily available o-aminobenzonitriles and aldehydes in water has been accomplished. I2/base and water play an unprecedented and vital role in the reaction. By electrochemically catalysed hydrolysis of o-aminobenzonitriles, the synthesis of quinazolinones with benzaldehyde was first proposed. The synthetic utility of this method was demonstrated by gram-scale operation, as well as the preparation of bioactive N-(2,5-dichlorophenyl)-6-(2,2,2-trifluoroethoxy) pteridin-4-amine, which enables straightforward, practical and environmentally benign quinazolinone formation.

Identification of blood-derived candidate gene markers and a new 7-gene diagnostic model for multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a central nervous system disease with a high disability rate. Modern molecular biology techniques have identified a number of key genes and diagnostic markers to MS, but the etiology and pathogenesis of MS remain unknown. RESULTS: In this study, the integration of three peripheral blood mononuclear cell (PBMC) microarray datasets and one peripheral blood T cells microarray dataset allowed comprehensive network and pathway analyses of the biological functions of MS-related genes. Differential expression analysis identified 78 significantly aberrantly expressed genes in MS, and further functional enrichment analysis showed that these genes were associated with innate immune response-activating signal transduction (p = 0.0017), neutrophil mediated immunity (p = 0.002), positive regulation of innate immune response (p = 0.004), IL-17 signaling pathway (p < 0.035) and other immune-related signaling pathways. In addition, a network of MS-specific protein-protein interactions (PPI) was constructed based on differential genes. Subsequent analysis of network topology properties identified the up-regulated CXCR4, ITGAM, ACTB, RHOA, RPS27A, UBA52, and RPL8 genes as the hub genes of the network, and they were also potential biomarkers of MS through Rap1 signaling pathway or leukocyte transendothelial migration. RT-qPCR results demonstrated that CXCR4 was obviously up-regulated, while ACTB, RHOA, and ITGAM were down-regulated in MS patient PBMC in comparison with normal samples. Finally, support vector machine was employed to establish a diagnostic model of MS with a high prediction performance in internal and external datasets (mean AUC = 0.97) and in different chip platform datasets (AUC = (0.93). CONCLUSION: This study provides new understanding for the etiology/pathogenesis of MS, facilitating an early identification and prediction of MS.

Constant-wavelength synchronous fluorescence spectrometry for simultaneous and rapid determination of five polycyclic aromatic hydrocarbon residues in dairy products.

A new method for simultaneously determining five polycyclic aromatic hydrocarbons (PAHs) (fluorene, benzofluorene, pyrene, benzo(a)pyrene, and perylene) in dairy products using constant-wavelength synchronous fluorescence spectrometry (CWSFS) was established in this study. Acetonitrile was chosen as the extraction solvent to extract the five PAHs from the dairy products, and an ultrasound extraction method was adopted. The supernatants were filtered using a 0.45-µm microporous filter membrane and concentrated to dryness with a nitrogen dryer. The extracts were then re-dissolved in cyclohexane for analysis. To overcome interference from the background matrix and between PAHs, the difference in wavelength (Δλ) at 40 nm was chosen for CWSFS scanning. With only one single scan, the five PAHs in dairy products could be distinguished and determined using the standard curve method without the need for previous chromatographic separation of the analyte solution. Detection limits of fluorene, benzofluorene, pyrene, benzo(a)pyrene, and perylene were 0.0051 µg·L-1 , 0.016 µg·L-1 , 0.021 µg·L-1 , 0.0056 µg·L-1 , and 0.0062 µg·L-1 , respectively. Recoveries were between 85.60% and 98.42%. These five PAHs in dairy products were determined with good results and therefore expected to be a routine detection method for PAHs in dairy products.

Association of Ambient air Pollution with risk of preeclampsia during pregnancy: a retrospective cohort study.

BACKGROUND: Ambient air pollution is becoming a serious environmental problem in China. The results were inconsistent on that air pollution was a risk factor of preeclampsia in pregnancy. METHODS: Total 116,042 pregnant women were enrolled from 22 hospitals in 10 cities of Hebei Province, China from January 1, 2015 to December 31, 2017. The parturients were divided into preeclampsia group (PE group) and non-preeclampsia group (non-PE group). The data of air pollutants, namely, particulate matter (PM)2.5, PM10, NO2, SO2, CO, O3 were collected from China Environmental Inspection Station. RESULTS: Among the 116,042 pregnant women, 2988 (2.57%) pregnant women were diagnosed with preeclampsia. The concentrations of exposed PM2.5, PM10, NO2 and O3 in the PE group were significantly higher than those in the non-PE group, and they were risk factors of the PE group in the first and second trimester of pregnancy respectively. The concentrations of exposed SO2 and CO in PE patients and non-PE women were not different, but high concentration of these air pollutants were risk factors to PE in the second trimester. CONCLUSION: The exposure to PM2.5, PM10, NO2, O3 were risk factors for preeclampsia in the first and second trimester of pregnancy, while only at high level, SO2 and CO were risk factors for preeclampsia in the second trimester of pregnancy.

Amlexanox attenuates experimental autoimmune encephalomyelitis by inhibiting dendritic cell maturation and reprogramming effector and regulatory T cell responses.

BACKGROUND: Amlexanox (ALX), a TBK1 inhibitor, can modulate immune responses and has anti-inflammatory properties. To investigate its role in regulating the progression of experimental autoimmune encephalomyelitis (EAE), we studied the effect of ALX on the maturation of dendritic cells (DCs) and the responses of effector and regulatory T cells (Tregs). METHODS: In vitro, bone marrow-derived DCs (BMDCs) were cultured and treated with ALX. Their proliferation, maturation, and their stimulatory function to induce T cells responses were detected. In vivo, the development of EAE from different groups was recorded. At the peak stage of disease, HE, LFB, and electronic microscope (EM) were used to evaluate inflammation and demyelination. Maturation of splenic DC and Th1/Th17/Treg response in the CNS and peripheral were also detected. To further explore the mechanism underlying the action of ALX in DC maturation, the activation of TBK1, IRF3, and AKT was analyzed. RESULTS: Our data indicated that ALX significantly inhibited the proliferation and maturation of BMDCs, characterized by the reduced MHCII, a co-stimulatory molecule, IL12, and IL-23 expression, along with morphological alterations. Co-culture of ALX-treated BMDCs inhibited allogeneic T cell proliferation and MOG-specific T cell response. In EAE mice, ALX significantly attenuated the EAE development by decreasing inflammatory infiltration and demyelination in the spinal cords, accompanied by reduced frequency of splenic pathogenic Th1 and Th17 cells and increased Tregs. Moreover, ALX treatment decreased Th1 and Th17 cytokines, but increased Treg cytokines in the CNS and spleen. Notably, ALX treatment reduced the frequency and expression of CD80 and CD86 on splenic DCs and lowered IL-12 and IL-23 secretion, further supporting an impaired maturation of splenic DCs. In addition, ALX potently reduced the phosphorylation of IRF3 and AKT in BMDC and splenic DCs, both of which are substrates of TBK1 and associated with DC maturation. CONCLUSIONS: ALX, a TBK1 inhibitor, mitigated EAE development by inhibiting DC maturation and subsequent pathogenic Th1 and Th17 responses while increasing Treg responses through attenuating the TBK1/AKT and TBK1/IRF3 signaling.

Rapamycin Ameliorates Experimental Autoimmune Encephalomyelitis by Suppressing the mTOR-STAT3 Pathway.

Rapamycin is a new immunosuppressant that has a primarily anti-inflammatory effect and selectively inhibits the activation of T helper (Th)-cell subsets. It is widely used to treat autoimmune disease. We studied the mechanism of rapamycin action against experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, a classic animal model of multiple sclerosis. Rapamycin significantly inhibited the development of EAE by decreasing both clinical scores and inflammatory cell infiltration into the spinal cord. Furthermore, rapamycin reversed EAE symptoms in mice showing the initial signs of paralysis. Rapamycin, is a mammalian target of rapamycin (mTOR) inhibitor. By measuring the downstream markers phospho-mTOR (p-mTOR)/mTOR and phospho-signal transducer and activator of transcription 3 (p-STAT3)/STAT3, we showed that rapamycin suppressed the mTOR-STAT3 pathway in EAE mice. The mTOR-STAT3 signaling pathway is important for Th1 and Th17 cell responses. We found that rapamycin-treated mice had reduced proportions of Th1 and Th17 cells, as well as lower mRNA expression for the transcription factors T-bet and RoRγt in EAE mouse splenocytes. To evaluate Th1 and Th17 cell function, we examined expression of their specific cytokines in the peripheral immune system and central nervous system. Rapamycin treatment reduced protein and mRNA levels of interferon (IFN)-γand interleukin (IL)-17 in splenocytes, and reduced IFN-γ and IL-17 mRNA levels in the spinal cords of EAE mice. These findings suggest that rapamycin treatment inhibits the mTOR-STAT3 pathway in EAE mice, thereby promoting immunosuppression. This study may provide new insight into the mechanism controlling rapamycin effects in multiple sclerosis.

Bottom-Up Defect Modification Through Oily-Allicin Modified Buried Interface Achieving Highly Efficient and Stable Perovskite Solar Cells.

The buried interface properties of the perovskite solar cells (PSCs) play a crucial role in the power conversion efficiency (PCE) and operational stability. The metal-oxide/perovskite heterogeneous interfaces are highly defective and cause serious ion migration. However, the buried and unexposed bottom interface and simultaneous stabilization of grain boundaries receive less attention and effective solutions. To tackle this problem, a solid-liquid strategy is employed by introducing oily-additive allicin at the buried interface to passivate the shallow (VI and Vo) and deep traps (VPb and PbI). Interestingly, oily status allicin fills the pinholes at the heterointerface and wraps the perovskite grains, suppressing the ion migration during the photoaging process. As a result, an outstanding PCE of 25.07% is achieved with a remarkable fill factor (FF) of 84.03%. The modified devices can maintain 94.51% of the original PCE after light soaking under 1-sun illumination for 1000 h. This work demonstrates a buried interface modification method that employs an eco-friendly additive, which helps promote the development of PSCs with high performance and stability.

Exosomal miR-128-3p reversed fibrinogen-mediated inhibition of oligodendrocyte progenitor cell differentiation and remyelination after cerebral ischemia.

AIMS: To investigate the role of exosomal miR-128-3p in promoting fibrinogen-mediated inhibition of oligodendrocyte progenitor cell (OPC) differentiation and the therapeutic potential of exosomal miR-128-3p in cerebral ischemia. METHODS: Mouse models of middle cerebral artery occlusion (MCAO) were established as described previously. MCAO was treated with fibrinogen and exosomes by stereotactically injecting into the left stratum. Mouse cortical OPCs were used for mRNA and miRNA sequencing analysis. Exosomes were isolated from neural stem cells (NSCs) of mice. RESULTS: Fibrinogen deposition suppressed remyelination after MCAO and inhibited OPC differentiation by activating ACVR1, the bone morphogenetic protein (BMP) signaling type I receptor. In vitro, miR-sequencing and verification studies revealed that miR-128-3p is associated with BMP signaling mediated by ACVR1. Additionally, transfer of NSC-derived exosomal miR-128-3p to OPCs significantly increased myelin basic protein expression and inhibited BMP signaling. Furthermore, NSC-derived exosomal miR-128-3p protected against fibrinogen-induced demyelination related to BMP signaling, reduced the infarct volume, and improved neurological function after MCAO. CONCLUSIONS: Fibrinogen deposition inhibits remyelination after ischemic damage and NSC-derived exosomal miR-128-3p promotes OPC differentiation into OLs by suppressing BMP signaling, indicating that NSC-derived exosomal miR-128-3p represents a potential therapeutic target for ischemic stroke.

Fibrinogen-to-Albumin Ratio and Clinical Outcomes in Patients With Large Artery Atherosclerosis Stroke.

BACKGROUND: A high fibrinogen-to-albumin ratio (FAR), a novel inflammatory marker, is considered to be a prognostic marker in vascular diseases. However, the association of FAR with large artery atherosclerosis (LAA) stroke is still unknown. This study was conducted to evaluate the association between FAR levels and clinical outcomes in patients with acute LAA stroke. METHODS AND RESULTS: A total of 809 patients within 72 hours of LAA stroke were included and followed up to 1 year. FAR was calculated as fibrinogen (g/L)/albumin (g/L). The associations of FAR with clinical outcomes were assessed by multivariate Cox regression or logistic regression analysis. Clinical outcomes included stroke recurrence, all-cause death, poor functional outcome (modified Rankin Scale score 3-6), and dependence (modified Rankin Scale score 3-5). Among the 809 patients with acute LAA stroke, the median FAR was 0.075 (interquartile range, 0.064-0.087). At 1 year, 103 (12.7%) patients had stroke recurrence, 105 (13.0%) had poor functional outcome, 76 (9.8%) had dependence, and 29 (3.6%) had died. After adjusting for all confounding risk factors, a high FAR level was associated with stroke recurrence (hazard ratio, 2.57 [95% CI, 1.32-5.02]), poor functional outcome (odds ratio, 3.30 [95% CI, 1.57-6.94]), and dependence (odds ratio, 3.49 [95% CI, 1.49-8.19]). CONCLUSIONS: A high FAR level was associated with an increased risk of stroke recurrence, poor functional outcome, and dependence in patients with acute LAA stroke.

One-step synthesis of well-defined molecularly imprinted nanospheres for the class-selective recognition and separation of ß-blockers in human serum.

ß-blockers are a class of medications that are used to treat abnormal heart rhythms and hypertension. Molecularly imprinted polymers (MIPs) capable of selective recognizing and extracting ß-blockers from complex biological samples hold great promise in bioanalytical and biomedical applications, but developing such artificial receptor materials is still challenging. Herein, we introduce a simple one-step method for the synthesis of well-defined molecularly imprinted nanospheres in high yield (83.6-94.4%) via reversible addition-fragmentation chain transfer (RAFT) precipitation polymerization for the selective recognition and extraction of the ß-blockers from human serum. The prepared MIPs are characterized in terms of morphology, pore properties, binding kinetics, capacity, selectivity, and recognition mechanisms. The uniform nanoscale-imprinted layer favored the rapid mass transfer of ß-blockers. The binding studies showed the high adsorption capacity (126.8 µmol/g) and selectivity of the developed nanomaterial. The investigation on the recognition mechanism reveals that multiple driving forces participate in the binding between MIP and ß-blockers, where hydrogen bonding plays as the dominating role for the specific recognition. The MIP was successfully applied for the direct enrichment of five ß-blockers from human serum with HPLC recoveries ranging from 82.9 to 100.3% and RSD of 0.5-6.9% (n = 3).

miRNA-29 aggravates myocardial infarction via inhibiting the PI3K/mTOR/HIF1α/VEGF pathway.

INTRODUCTION: MI is defined by the presence of myocardial necrosis, which is caused by acute and persistent ischemia and hypoxia of the coronary artery. In recent years, its incidence rate has been on the rise in China. METHODS: GSE34198, GSE97320 and GSE141512 datasets were download for DEG analysis. KEGG pathway analysis, GO analysis, GSEA and PPI network construction were performed. Later, target genes of candidate miRNAs were predicted. Next, echocardiography was conducted to detect the effects of miR-29 on left ventricular structure and cardiac function in vivo, and H&E staining was adopted to study the effects of miR-29 on angiogenesis and fibrosis in vivo. Furthermore, Western blotting was employed to investigate the effects of miR-29 inhibition on the expressions of proteins related to the PI3K\mTOR\ HIF-1α\VEGF pathway. RESULTS: There were 162 DEGs involved in MI. GO analysis revealed that inflammatory responses, negative regulation of apoptosis and innate immune response were the main enriched biological processes. KEGG analysis manifested that DEGs were mainly enriched in the PI3K/Akt signaling pathway, and GSEA demonstrated that they were mainly enriched in the PI3K/Akt/mTOR, HIF and VEGF pathways. Moreover, target gene prediction showed that miR-29 was lowly expressed in MI. According to Masson's trichrome staining, miR-29 inhibition promoted angiogenesis, reduced fibrosis, and increased the protein expressions of p-PI3K, p-mTOR, HIF-1α, and VEGF. CONCLUSIONS: MiR-29 may play an important role in the growth and development of MI. After inhibition of miR-29, the PI3K/mTOR/HIF-1α/VEGF pathway is activated to alleviate MI.

Changes in the BTK/NF-κB signaling pathway and related cytokines in different stages of neuromyelitis optica spectrum disorders.

OBJECTIVE: Neuromyelitis optica spectrum disorders (NMOSDs) are blindness-causing neuritis; their pathogenesis is still not fully elucidated. Although it has been determined that Bruton tyrosine kinase (BTK) and NF-κB are associated with NMOSD, the changes that occur in different periods remain unknown. The study aimed to demonstrate the changes in the BTK/NF-κB pathway and related chemokines in different stages of NMOSDs. METHODS: A total of 32 patients with NMOSD were selected as the experimental group, and 32 healthy volunteers were included in the control group. In this study, the BTK/NF-κB pathway and related chemokines in the cerebrospinal fluid and peripheral blood samples of patients with NMOSD were analyzed in the acute or remission phase. RESULTS: BTK, NF-κB, PI3K, IKK, CXCL2, and CXCL12 levels in the NMOSD group in the acute or remission phase were significantly higher than those in the control group (p < 0.05). CONCLUSION: The BTK/NF-κB pathway plays a vital role in the progression of NMOSD pathology. Our results shed light on its important role as a therapeutic target for NMOSD.

DIPEA-induced activation of OH- for the synthesis of amides via photocatalysis.

The development of green protocols for photocatalysis where water acts as a nucleophile, induced by a weak organic base, is difficult to achieve in organic chemistry. Herein, an efficient light-mediated strategy for the synthesis of amides in which a weak organic base acts as a reductant to induce the formation of OH- from water under metal-free conditions is reported. A mechanistic study reveals that the generation of an N,N-diisopropylethylamine (DIPEA) radical via single electron transfer (SET), with the assistance of photocatalyst, that increases the nucleophilicity of the water molecules with respect to the cyanides is essential. Moreover, the removal rate of nitrile in wastewater can be as high as 83%, indicating that this strategy has excellent potential for nitrile degradation.

Non-metal-mediated N-oxyl radical (TEMPO)-induced acceptorless dehydrogenation of N-heterocycles via electrocatalysis.

The development of protocols for direct catalytic acceptorless dehydrogenation of N-heterocycles with metal-free catalysts holds the key to difficulties in green and sustainable chemistry. Herein, an N-oxyl radical (TEMPO) acting as an oxidant in combination with electrochemistry is used as a synthesis system under neutral conditions to produce N-heterocycles such as benzimidazole and quinazolinone. The key feature of this protocol is the utilization of the TEMPO system as an inexpensive and easy to handle radical surrogate that can effectively promote the dehydrogenation reaction. Mechanistic studies also suggest that oxidative TEMPOs redox catalytic cycle participates in the dehydrogenation of 2,3-dihydro heteroarenes.

Plasma Levels of Homocysteine is Associated with Liver Fibrosis in Health Check-Up Population.

OBJECT: Studies have shown a link between homocysteine (Hcy) and heart diseases, kidney diseases, cerebrovascular diseases, liver diseases, and other pathological conditions. However, the relationship between Hcy and liver fibrosis (LF) is unclear. Here, we studied the link between plasma Hcy concentration and LF. METHODS: We determined and recorded the plasma Hcy concentration, general biochemical parameters, and liver stiffness measurement (LSM) in 1582 subjects, followed by statistical data analyses. RESULTS: During different stages of LF, we found a considerable difference (p <0.001 unless specified) in body mass index (BMI), sex, age, Hcy, the levels of alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT; P = 0.012), triglycerides (TG; P = 0.006), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBS), and platelet count (PLT). There was a strong association between the plasma Hcy concentration and the serum biomarkers of LF (P <0.001) and the values of LSM (P <0.001). CONCLUSION: The plasma Hcy concentration was substantially different among different stages of LF. The higher the plasma Hcy concentration, the more evident was the degree of LF.

Electro-oxidative cyclization: access to quinazolinones via K2S2O8 without transition metal catalyst and base.

A K2S2O8-promoted oxidative tandem cyclization of primary alcohols with 2-aminobenzamides to synthesize quinazolinones was successfully achieved under undivided electrolytic conditions without a transition metal and base. The key feature of this protocol is the utilization of K2S2O8 as an inexpensive and easy-to-handle radical surrogate that can effectively promote the reaction via a simple procedure, leading to the formation of nitrogen heterocycles via direct oxidative cyclization at room temperature in a one-pot procedure under constant current. Owing to the use of continuous-flow electrochemical setups, this green, mild and practical electrosynthesis features high efficiency and excellent functional group tolerance and is easy to scale up.

Association of Level and Increase in D-Dimer With All-Cause Death and Poor Functional Outcome After Ischemic Stroke or Transient Ischemic Attack.

Background D-dimer is involved in poor outcomes of stroke as a coagulation biomarker. We aimed to investigate the associations of the level and increase in D-dimer between baseline and 90 days with all-cause death or poor functional outcome in patients after ischemic stroke or transient ischemic attack. Methods and Results We collected data from the CNSRIII (Third China National Stroke Registry) study. The present substudy included 10 518 patients within 7 days (baseline) of ischemic stroke or transient ischemic attack and 6268 patients at 90 days. Poor functional outcome at 1 year was assessed on the basis of the modified Rankin Scale (≥3). Multivariable Cox regression or logistic regression was used to assess the association of D-dimer levels with all-cause death or poor functional outcome. D-dimer levels at 90 days were lower than those at baseline (1.4 µg/mL versus 1.7 µg/mL; P<0.001). Higher baseline D-dimer level was associated with all-cause death (adjusted hazard ratio [HR], 1.77; 95% CI, 1.25-2.52; P=0.001) and poor functional outcome (adjusted odds ratio [OR], 1.49; 95% CI, 1.23-1.80; P<0.001) during 1-year follow-up. Higher D-dimer level at 90 days was also associated with poor outcomes independently. Furthermore, an increase in D-dimer levels between baseline and 90 days was associated with all-cause death (since 90 days to 1 year after index event) (adjusted HR, 1.99; 95% CI, 1.12-3.53; P=0.019) but not with poor functional outcome (adjusted OR, 1.08; 95% CI, 0.82-1.41). Conclusions Our study shows that high level and an increase in D-dimer between baseline and 90 days are associated with poor outcomes in patients after ischemic stroke or transient ischemic attack.

Selective recognition of a cyclic peptide hormone in human plasma by hydrazone bond-oriented surface imprinted nanoparticles.

As a kind of artificial recognition material, molecularly imprinted polymers (MIPs) offer a promising perspective to be developed as synthetic chemical binders capable of selectively recognize biomacromolecules. However, owing to the large size and conformational flexibility of proteins and peptides, imprinting of these biomacromolecules remains a challenge. Novel imprinting strategies still need exploration for the improvement of recognition performance of MIPs. Herein, we developed a hydrazone bond-oriented surface imprinting strategy for an endogenous peptide hormone, human atrial natriuretic peptide (ANP). Surface-oriented imprinting of peptide via reversible covalent bond anchoring approach increased the orientation homogeneity of imprinted cavities as well as the utility of templates. The prepared nanoparticles exhibited high selectivity and fast recognition kinetics for ANP epitope. The dissociation constant between ANP epitope and MIP was measured as 5.3 µM. The applicability of the material in real samples was verified by the selective magnetic extraction of ANP from human plasma samples. This hydrazone bond-oriented surface imprinting strategy provides an alternative approach for the separation of peptides or proteins in complex bio-samples.