Highly Sensitive Surface-Enhanced Raman Scattering Sensing of Heparin Based on Antiaggregation of Functionalized Silver Nanoparticles

We report a simple and sensitive surface-enhanced Raman scattering (SERS) platform for the detection of heparin, based on antiaggregation of 4-mercaptopyridine (4-MPY) functionalized silver nanoparticles (Ag NPs). Here, protamine was employed as a medium for inducing the aggregation of negatively charged 4-MPY functionalized Ag NPs through surface electrostatic interaction, which resulted in significantly enhanced Raman signal of the Raman reporter. However, in the presence of heparin, the interaction between heparin and protamine decreased the concentration of free protamine, which dissipated the aggregated 4-MPY functionalized Ag NPs and thus decreased Raman enhancement effect. The degree of aggregation and Raman enhancement effect was proportional to the concentration of added heparin. Under optimized assay conditions, good linear relationship was obtained over the range of 0.5-150 ng/mL (R-2 = 0.998) with a minimum detectable concentration of 0.5 ng/mL in standard aqueous solution. Furthermore, the developed method was also successfully applied for detecting heparin in fetal bovine serum samples with a linear range of 1-400 ng/mL.We report a simple and sensitive surface-enhanced Raman scattering (SERS) platform for the detection of heparin, based on antiaggregation of 4-mercaptopyridine (4-MPY) functionalized silver nanoparticles (Ag NPs). Here, protamine was employed as a medium for inducing the aggregation of negatively charged 4-MPY functionalized Ag NPs through surface electrostatic interaction, which resulted in significantly enhanced Raman signal of the Raman reporter. However, in the presence of heparin, the interaction between heparin and protamine decreased the concentration of free protamine, which dissipated the aggregated 4-MPY functionalized Ag NPs and thus decreased Raman enhancement effect. The degree of aggregation and Raman enhancement effect was proportional to the concentration of added heparin. Under optimized assay conditions, good linear relationship was obtained over the range of 0.5-150 ng/mL (R-2 = 0.998) with a minimum detectable concentration of 0.5 ng/mL in standard aqueous solution. Furthermore, the developed method was also successfully applied for detecting heparin in fetal bovine serum samples with a linear range of 1-400 ng/mL

Enhanced Neuroprotective Effects by Inter-Ischemia Hypothermia in Cerebral Stroke

Background and Purpose. Studies have shown that inter-ischemia hypothermia is able to reduce the size of myocardial infarctions and improve their clinical outcomes. The present study determined whether inter-ischemia hypothermia induced by pharmacological approach induced stronger neuroprotection in ischemic brains. Methods. Adult male Sprague-Dawley rats were studied in 4 groups: (1) sham; (2) stroke; (3) stroke treated with pharmacological hypothermia before reperfusion (inter-ischemia hypothermia); and (4) stroke treated with pharmacological hypothermia after reperfusion is initiated (inter-reperfusion hypothermia). The combination of chlorpromazine and promethazine with dihydrocapsaicin was used to induce hypothermia. To compare the neuroprotective effects of drug-induced hypothermia between the groups, brain damage was evaluated using infarct volume and neurological deficits. In addition, mRNA expressions of NADPH oxidase subunits and glucose transporter subtypes were determined by real-time PCR. ROS production was measured by Flow cytometry assay at the same time points. Results: In both hypothermia groups, cerebral infarct volumes and neurological deficits were reduced. ROS production and the expressions of NOX subunits and glucose transporter subtypes were also significantly reduced in both hypothermia groups as compared to the ischemic group. While there were no statistically significant differences between the two hypothermia groups at 6 h reperfusion, brain damage was significantly further decreased by inter-ischemia hypothermia at 24 h. Conclusion: Inter-ischemia hypothermia and inter-reperfusion hypothermia after stroke induced neuroprotection by reducing oxidative injury, while neuroprotion was more effective with inter-ischemia hypothermia. This study provides a new avenue and reference for a stronger neuroprotective hypothermia before vascular recanalization in stroke patients

Hypothermia in Stroke Therapy: Systemic versus Local Application

Presently, there are no effective, widely applicable therapies for ischemic stroke. There is strong clinical evidence for the neuroprotective benefits of hypothermia, and surface-cooling methods have been utilized for decades in the treatment of cerebral ischemia during cardiac arrest, but complications with hypothermia induction have hindered its clinical acceptance in ischemic stroke therapy. Recently, the microcatheter-based local endovascular infusion (LEVI) of cold saline directly to the infarct site has been proposed as a solution to the drawbacks of surface cooling. The safety and efficacy of LEVI in rat models have been established, and implementation in larger animals has been similarly encouraging. A recent pilot study even established the safety of LEVI in humans. This review seeks to outline the major research on LEVI, discusses the mechanisms that mediate its superior neuroprotection over surface and systemic cooling, and identifies areas that warrant further investigation. While LEVI features improvements on surface cooling, its core mechanisms of neuroprotection are still largely shared with therapeutic hypothermia in general. As such, the mechanisms of hypothermia-based neuroprotection are discussed as well

Quantifying evolution of soot mixing state from transboundary transport of biomass burning emissions

Incomplete combustion of fossil fuels and biomass burning emit large amounts of soot particles into the troposphere. The condensation process is considered to influence the size (Dp) and mixing state of soot particles, which affects their solar absorption efficiency and lifetimes. However, quantifying aging evolution of soot remains hampered in the real world because of complicated sources and observation technologies. In the Himalayas, we isolated soot sourced from transboundary transport of biomass burning and revealed soot aging mechanisms through microscopic observations. Most of coated soot particles stabilized one soot core under Dp &lt; 400 nm, but 34.8% of them contained multi-soot cores (nsoot ≥ 2) and nsoot increased 3–9 times with increasing Dp. We established the soot mixing models to quantify transformation from condensation- to coagulation-dominant regime at Dp ≈ 400 nm. Studies provide essential references for adopting mixing rules and quantifying the optical absorption of soot in atmospheric models.</p

High Intensity Physical Rehabilitation Later Than 24 h Post Stroke Is Beneficial in Patients: A Pilot Randomized Controlled Trial (RCT) Study in Mild to Moderate Ischemic Stroke

Objective: Very early mobilization was thought to contribute to beneficial outcomes in stroke-unit care, but the optimal intervention strategy including initiation time and intensity of mobilization are unclear. In this study, we sought to confirm the rehabilitative effects of different initiation times (24 vs. 48 h) with different mobilization intensities (routine or intensive) in ischemic stroke patients within three groups.Materials and Methods: We conducted a randomized and controlled trial with a blinded follow-up assessment. Patients with ischemic stroke, first or recurrent, admitted to stroke unit within 24 h after stroke onset were recruited. Eligible subjects were randomly assigned (1:1:1) to 3 groups: Early Routine Mobilization in which patients received &lt; 1.5 h/d out-of-bed mobilization within 24–48 h after stroke onset, Early Intensive Mobilization in which patients initiated ≥3 h/d mobilization at 24–48 h after the stroke onset, and Very Early Intensive Mobilization in which patients received≥3 h/d mobilization within 24 h. The modified Rankin Scale score of 0–2 was used as the primary favorable outcome.Results: We analyzed 248 of the 300 patients (80 in Early Routine Mobilization, 82 in Very Early Intensive Mobilization and 86 in Early Intensive Mobilization), with 52 dropping out (20 in Early Routine Mobilization, 18 in Very Early Intensive Mobilization and 14 in Early Intensive Mobilization). Among the three groups, the Early Intensive Mobilization group had the most favorable outcomes at 3-month follow-up, followed by patients in the Early Routine Mobilization group. Patients in Very Early Intensive Mobilization received the least odds of favorable outcomes. At 3 month follow up, 53.5%, (n = 46) of patients with Early Intensive Mobilization showed a favorable outcome (modified Rankin Scale 0–2) (p = 0.041) as compared to 37.8% (n = 31) of patients in the Very Early Intensive Mobilization.Conclusions: Post-stroke rehabilitation with high intensity physical exercise at 48 h may be beneficial. Very Early Intensive Mobilization did not lead to a favorable outcome at 3 months.Clinical Trial Registration:www.chictr.org.cn, identifier ChiCTR-ICR-15005992

Phytoplankton community structure in the Western Subarctic Gyre of the Pacific Ocean during summer determined by a combined approach of HPLC-pigment CHEMTAX and metabarcoding sequencing

The Western Subarctic Gyre (WSG) is a cyclonic upwelling gyre in the northwest subarctic Pacific, which is a region with a high concentration of nutrients but low chlorophyll. We investigated the community structure and spatial distribution of phytoplankton in this area by using HPLC-pigment CHEMTAX (a chemotaxonomy program) and metabarcoding sequencing during the summer of 2021. The phytoplankton community showed significant differences between the two methods. The CHEMTAX analyses identified eight major marine phytoplankton assemblages. Cryptophytes were the major contributors (24.96%) to the total Chl a, followed by pelagophytes, prymnesiophytes, diatoms, and chlorophytes. The eukaryotic phytoplankton OTUs obtained by metabarcoding were categorized into 149 species in 96 genera of 6 major groups (diatoms, prymnesiophytes, pelagophytes, chlorophytes, cryptophytes, and dinoflagellates). Dinoflagellates were the most abundant group, accounting for 44.74% of the total OTUs obtained, followed by cryptophytes and pelagophytes. Sixteen out of the 97 identified species were annotated as harmful algal species, and Heterocapsa rotundata, Karlodinium veneficum, and Aureococcus anophagefferens were assigned to the abundant group (i.e., at least 0.1% of the total reads). Nutrients were more important in shaping the phytoplankton community than temperature and salinity. The 24 stations were divided into southern and northern regions along 44°N according to the k-means method, with the former being dominated by high Chl a and low nutrients. Although different phytoplankton assemblages analyzed by the two methods showed various relationships with environmental factors, a common feature was that the dinoflagellate proportion showed a significantly negative correlation with low nutrients and a positive correlation with Chl a

Atmospheric deposition and river runoff stimulate the utilization of dissolved organic phosphorus in coastal seas

In coastal seas, the role of atmospheric deposition and river runoff in dissolved organic phosphorus (DOP) utilization is not well understood. Here, we address this knowledge gap by combining microcosm experiments with a global approach considering the relationship between the activity of alkaline phosphatases and changes in phytoplankton biomass in relation to the concentration of dissolved inorganic phosphorus (DIP). Our results suggest that the addition of aerosols and riverine water stimulate the biological utilization of DOP in coastal seas primarily by depleting DIP due to increasing nitrogen concentrations, which enhances phytoplankton growth. This “Anthropogenic Nitrogen Pump” was therefore identified to make DOP an important source of phosphorus for phytoplankton in coastal seas but only when the ratio of chlorophyll a to DIP [Log10 (Chl a / DIP)] is larger than 1.20. Our study therefore suggests that anthropogenic nitrogen input might contribute to the phosphorus cycle in coastal seas

Large vessel occlusion stroke outcomes in diabetic vs. non-diabetic patients with acute stress hyperglycemia

ObjectiveThis study assesses whether stress-induced hyperglycemia is a predictor of poor outcome at 3 months for patients with acute ischemic stroke (AIS) treated by endovascular treatment (EVT) and impacted by their previous blood glucose status.MethodsThis retrospective study collected data from 576 patients with AIS due to large vessel occlusion (LVO) treated by EVT from March 2019 to June 2022. The sample was composed of 230 and 346 patients with and without diabetes mellitus (DM), respectively, based on their premorbid diabetic status. Prognosis was assessed with modified Rankin Scale (mRS) at 3-month after AIS. Poor prognosis was defined as mRS&gt;2. Stress-induced hyperglycemia was assessed by fasting glucose-to-glycated hemoglobin ratio (GAR). Each group was stratified into four groups by quartiles of GAR (Q1–Q4). Binary logistic regression analysis was used to identify relationship between different GAR quartiles and clinical outcome after EVT.ResultsIn DM group, a poor prognosis was seen in 122 (53%) patients and GAR level was 1.27 ± 0.44. These variables were higher than non-DM group and the differences were statistically significant (p &lt; 0.05, respectively). Patients with severe stress-induced hyperglycemia demonstrated greater incidence of 3-month poor prognosis (DM: Q1, 39.7%; Q2, 45.6%; Q3, 58.6%; Q4, 68.4%; p = 0.009. Non-DM: Q1, 31%; Q2, 32.6%; Q3, 42.5%; Q4, 64%; p &lt; 0.001). However, the highest quartile of GAR was independently associated with poor prognosis at 3 months (OR 3.39, 95% CI 1.66–6.96, p = 0.001), compared to the lowest quartile in non-DM patients after logistic regression. This association was not observed from DM patients.ConclusionThe outcome of patients with acute LVO stroke treated with EVT appears to be influenced by premorbid diabetes status. However, the poor prognosis at 3-month in patients with DM is not independently correlated with stress-induced hyperglycemia. This could be due to the long-term damage of persistent hyperglycemia and diabetic patients’ adaptive response to stress following acute ischemic damage to the brain

Contrôle des propriétés magnéto-optiques de systèmes magnétoplasmoniques grâce à la nanostructuration

This PhD dissertation deals with the tuning of the magneto-optical (MO) response of three different magnetoplasmonic systems by using different nanostructuration schemes. They are structures based on SPPs, LSPs and RIfS, respectively. The manipulation of MO activity to be used in biosensors and to improve the sensitivity is also discussed. The first system is thin-film SPP structure consisting of magnetic and plasmonic layers, where the magnetic part is nanostructured multilayers with controlled uni-axial anisotropy. The uni-axial anisotropic properties of the multilayered magnetic materials were clearly reflected on the plasmonic properties of the system. An enhancement in the MO activity can be used to improve the sensitivity of the sensors based on this structure. The second system is a LSP-based magnetoplasmonic structure consisting of Au nanoparticle arrays and continuous magnetic layers. It is demonstrated that a dielectric layer in between Au nanoparticles and ferromagnetic layers is indispensable in order to preserve the plasmonic resonance. The thickness of magnetic layers has an effect on the plasmonic property, which can be further used to tune the MO activity. The third system is a hybrid RIfS structure with a magnetoplasmonic multilayer Ag/ITO/CoFeB/ITO/Ag deposited on a nanoporous AAO substrate. The RIfS signal depends on both the size and the length of the nanopores. The diameter of the nanopores also affects the MO response by generating a reversal in the sign of the Kerr loops. This can be viewed as the tuning factor of MO activity of the structure.Ce travail de thèse porte sur le contrôle des propriétés de trois systèmes magnéto-plasmoniques grâce à différents types de nanostructuration. Ces structures sont basées respectivement sur la Propagation de Plasmons de Surface (SPP), les Plasmons de Surface Localisés (LSP) et la spectroscopie d’interférences en réflexion (RIfS). La manipulation des propriétés magnéto-optiques (MO) pour une utilisation dans les biocapteurs est discutée. Le premier système est une structure SPP en couche mince de couches de métaux nobles et d’un matériau magnétique de type multicouche présentant une anisotropie uni-axiale contrôlée. L’anisotropie de la couche magnétique se reflète sur les propriétés plasmoniques. Une amélioration de l’activité magnéto-optique peut être mise à profit pour améliorer la sensibilité de capteurs basés sur cette structure. Le second dispositif est une structure LSP avec nanoparticules d’or et d’une couche magnétique continue. Il est démontré qu’une couche diélectrique entre la couche magnétique et les nanoparticules d’or est indispensable pour préserver la résonance plasmonique. L’épaisseur de la couche magnétique a un effet sur cette dernière qui peut en principe être mise à profit pour influer sur l’activité magnéto-optique. La troisième approche est une structure RIfS composée d’un système multicouche magnéto-plasmonique Ag/ITO/CoFeB/ITO/Ag déposé sur un substrat nanoporeux d’oxyde d’aluminium anodique (AAO). Le signal RIfS dépend de la taille et de la longueur des nanopores. Le diamètre des nanopores affecte également la réponse magnéto-optique en réflexion en générant une inversion du signe des cycles d’aimantation mesurés par effet Kerr

Tailoring magneto-optical properties of magnetoplasmonic systems through nanostructuration

Ce travail de thèse porte sur le contrôle des propriétés de trois systèmes magnéto-plasmoniques grâce à différents types de nanostructuration. Ces structures sont basées respectivement sur la Propagation de Plasmons de Surface (SPP), les Plasmons de Surface Localisés (LSP) et la spectroscopie d’interférences en réflexion (RIfS). La manipulation des propriétés magnéto-optiques (MO) pour une utilisation dans les biocapteurs est discutée. Le premier système est une structure SPP en couche mince de couches de métaux nobles et d’un matériau magnétique de type multicouche présentant une anisotropie uni-axiale contrôlée. L’anisotropie de la couche magnétique se reflète sur les propriétés plasmoniques. Une amélioration de l’activité magnéto-optique peut être mise à profit pour améliorer la sensibilité de capteurs basés sur cette structure. Le second dispositif est une structure LSP avec nanoparticules d’or et d’une couche magnétique continue. Il est démontré qu’une couche diélectrique entre la couche magnétique et les nanoparticules d’or est indispensable pour préserver la résonance plasmonique. L’épaisseur de la couche magnétique a un effet sur cette dernière qui peut en principe être mise à profit pour influer sur l’activité magnéto-optique. La troisième approche est une structure RIfS composée d’un système multicouche magnéto-plasmonique Ag/ITO/CoFeB/ITO/Ag déposé sur un substrat nanoporeux d’oxyde d’aluminium anodique (AAO). Le signal RIfS dépend de la taille et de la longueur des nanopores. Le diamètre des nanopores affecte également la réponse magnéto-optique en réflexion en générant une inversion du signe des cycles d’aimantation mesurés par effet Kerr.This PhD dissertation deals with the tuning of the magneto-optical (MO) response of three different magnetoplasmonic systems by using different nanostructuration schemes. They are structures based on SPPs, LSPs and RIfS, respectively. The manipulation of MO activity to be used in biosensors and to improve the sensitivity is also discussed. The first system is thin-film SPP structure consisting of magnetic and plasmonic layers, where the magnetic part is nanostructured multilayers with controlled uni-axial anisotropy. The uni-axial anisotropic properties of the multilayered magnetic materials were clearly reflected on the plasmonic properties of the system. An enhancement in the MO activity can be used to improve the sensitivity of the sensors based on this structure. The second system is a LSP-based magnetoplasmonic structure consisting of Au nanoparticle arrays and continuous magnetic layers. It is demonstrated that a dielectric layer in between Au nanoparticles and ferromagnetic layers is indispensable in order to preserve the plasmonic resonance. The thickness of magnetic layers has an effect on the plasmonic property, which can be further used to tune the MO activity. The third system is a hybrid RIfS structure with a magnetoplasmonic multilayer Ag/ITO/CoFeB/ITO/Ag deposited on a nanoporous AAO substrate. The RIfS signal depends on both the size and the length of the nanopores. The diameter of the nanopores also affects the MO response by generating a reversal in the sign of the Kerr loops. This can be viewed as the tuning factor of MO activity of the structure