Study of cell and drug interactions based on dual-mode detection using SPR and fluorescence imaging.

The investigation of the interactions between cells and drugs forms a crucial aspect of biological and clinical medical studies. Generally, single-cell or local-cellular studies require a microscopic imaging system with high magnifications, which suffers from low detection throughputs and poor time responses. The study presented in this paper combined SPR and fluorescence to achieve cell localization, real-time monitoring of cell images and quantitative analysis of drugs. In order to obtain more comprehensive, accurate and real-time data, a dual-mode system based on surface plasmon resonance (SPR) and fluorescence was constructed based on a 4× magnification lens. This enables simultaneous studies of an entire cell and a specific region of the cell membrane. An adaptive adjustment algorithm was established for distorted SPR images, achieving temporal and spatial matching of the dual-mode detection. The combination of SPR and fluorescence not only achieved micro-detection but also complemented the qualitative or quantitative limitations of SPR or fluorescence method alone. In system characterization, the response signal of SPR was noticed to increase with the increasing concentration of EGF in stimulated cells. It indicated that this platform could be employed for quantitative detection of the cell membrane region. Upon addition of EGF, a peak in the SPR curve was observed, and the cells in the corresponding SPR image turned whiter. This indicated that the platform can simultaneously monitor the SPR response signal and image changes. The response time of fluorescence in EGF testing was several seconds earlier than SPR, revealing that signal transduction first occurred in the whole cell and then propagated to the cell membrane region. The inhibitory ability of Gefitinib on cells was verified in a fast and real-time manner within 20 min. The results indicated that the detection limit of this method was 20 IU/mL for EGF and 10 µg/mL for Gefitinib. In conclusion, this study demonstrates the advantages of SPR and fluorescence dual-mode techniques in the analysis of cell-drug interactions, as well as their strong potential in drug screening.

PtNPs/PEDOT:PSS-Modified Microelectrode Arrays for Detection of the Discharge of Head Direction Cells in the Retrosplenial Cortex of Rats under Dissociation between Visual and Vestibular Inputs.

The electrophysiological activities of head direction (HD) cells under visual and vestibular input dissociation are important to understanding the formation of the sense of direction in animals. In this paper, we fabricated a PtNPs/PEDOT:PSS-modified MEA to detect changes in the discharge of HD cells under dissociated sensory conditions. The electrode shape was customized for the retrosplenial cortex (RSC) and was conducive to the sequential detection of neurons at different depths in vivo when combined with a microdriver. The recording sites of the electrode were modified with PtNPs/PEDOT:PSS to form a three-dimensional convex structure, leading to closer contact with neurons and improving the detection performance and signal-to-noise ratio of the MEA. We designed a rotating cylindrical arena to separate the visual and vestibular information of the rats and detected the changes in the directional tuning of the HD cells in the RSC. The results showed that after visual and vestibular sensory dissociation, HD cells used visual information to establish newly discharged directions which differed from the original direction. However, with the longer time required to process inconsistent sensory information, the function of the HD system gradually degraded. After recovery, the HD cells reverted to their newly established direction rather than the original direction. The research based on our MEAs revealed how HD cells process dissociated sensory information and contributes to the study of the spatial cognitive navigation mechanism.

Telomere length and multiple sclerosis: a Mendelian randomization study.

PURPOSE OF THE STUDY: Previous studies have established that telomere length is associated with multiple sclerosis (MS). However, confounding factors and reverse causality bias can impair observational research. Here, we conducted a two-sample MR study to see if telomere length is causally linked to MS using publically available GWAS summary statistics. MATERIALS AND METHODS: We screened 13 independent single-nucleotide polymorphisms (SNPs) related to leukocyte telomere length in a recent genome-wide association meta-analysis, which was available for 78,592 samples of European ancestry. The summary statistics for MS were from the latest meta-analyses conducted by the International Multiple Sclerosis Genetics Consortium (IMSGC), which included 115,803 European participants (47,429 MS, 68,374 controls). RESULTS: We found that leukocyte telomere length and MS are correlated (IVW estimate of odds ratio (OR): 2.13 per 1-SD increase in genetically determined telomere length, 95% confidence interval (CI): 1.55-2.92, p = 3.18 × 10-6). CONCLUSION: Our MR study supported that leukocyte telomere length and MS have a positive causal relationship. Further researches are warranted to elucidate the physiological mechanism.

Correlation between neutrophil-to-lymphocyte ratio and stability of carotid plaques.

OBJECTIVE: The neutrophil-to-lymphocyte ratio (NLR) has been proved to be a strong predictor of carotid atherosclerotic plaque, but the correlation between NLR and the stability of carotid plaque is not clear. Thus we conducted a study to evaluate the correlation between NLR and the stability of carotid atherosclerotic plaque, and to develop a new evaluation scale for rapid clinical evaluation of carotid plaque stability. METHODS: We recruited 528 patients with acute anterior circulation ischemic stroke who were in accordance with extracranial and intracranial large artery atherosclerosis of Chinese ischemic stroke subtype. Blood routine examination and carotid ultrasound examination were performed on admission. According to the ultrasonic characteristics, the patients were divided into plaque stabilization group and plaque instability group. RESULTS: There was significant difference in NLR between plaque stability and instability groups (P < 0.001). The risk of plaque instability increased with the increase of NLR (odds ratio (OR), 4.737; 95% confidence interval (CI), 3.404-6.592; P < 0.001). Receiver operating characteristic (ROC) curve showed that the critical point of NLR is 2.55 and the area under the curve (AUC) was 0.782 (95%CI, 0.740-0.823; P < 0.001). The best cut-off value of the evaluation scale was ≥ 4 points (sensitivity, 0.77; specificity, 0.75; accuracy, 0.76). CONCLUSION: There is a correlation between NLR and carotid plaque instability. NLR may be useful as a potential inflammation biomarker indicating the risk of unstable carotid plaques. The new scoring scale is a reliable index to predict the stability of carotid plaque.

Daytime sleepiness and risk of stroke: A Mendelian randomization analysis.

OBJECTIVE: Daytime sleepiness is known to be related to stroke, but whether daytime sleepiness is a risk factor for stroke remains unclear. We conducted a two-sample Mendelian randomization study to assess the relationship between daytime sleepiness and stroke, ischemic stroke (IS) and IS subtypes. METHODS: Thirty-six single-nucleotide polymorphisms (SNPs) associated with daytime sleepiness were selected as instrumental variables, which were identified from a recent genome-wide association study(N = 452,071). Summary statistics of the SNPs on stroke, IS and IS subtypes were derived from the MEGASTROKE consortium with 40,585 stroke cases and 406,111 controls. RESULTS: We found that daytime sleepiness was associated with large artery stroke (OR, 6.75; 95%CI, 1.49-30.57; p = 0.013), but not with all stroke (OR, 1.29; 95%CI, 0.81-2.05; p = 0.282), all ischemic stroke(OR, 1.46; 95%CI, 0.90-2.39; p = 0.136), cardioembolic stroke(OR, 1.0; 95%CI, 0.39-2.64; p = 0.984), or small artery stroke(OR, 1.52; 95%CI, 0.46-5.05; p = 0.485). CONCLUSION: Our findings indicated that daytime sleepiness is causally associated with an increased risk of large artery stroke. Further studies are necessary to verify our results and explain the physiological mechanisms.

The ability of Micropure® ultrasound technique to identify microcalcifications in carotid plaques.

OBJECTIVES: To study the ability of Micropure® ultrasound technique to identify microcalcifications in carotid plaques. METHODS: Forty-four carotids in 22 patients were enrolled in this study and were detected by routine ultrasound examination and Micropure® examination at the same time to identify microcalcifications in plaques. The results were compared with the tissue-background ratio (TBR) in 18F-NaF PET-CT imaging, which was performed one or two days after the ultrasound examination. RESULTS: In the 44 carotids, plaques were detected in 37 carotids. Microcalcifications were detected by the Micropure® technique in 32 carotids, which were located surrounded by macrocalcifications in 23 carotids, in the fibre cap in 12 carotids, and in the base of the plaque in 6 carotids. Microcalcifications were not detected in 12 carotids. In 18F-NaF PET-CT examination, TBR > 1.61 (range 1.62-3.99, mean 2.25 ± 0.58) was detected in 37 carotids, and TBR < 1.61 was detected in 7 carotids. There were no significant differences between the two methods in detecting microcalcifications (p = 0.180). The sensitivity of the Micropure® technique in detecting microcalcifications was 81.08 %, and the specificity was 71.43 %. CONCLUSIONS: Microcalcifications in the carotid artery detected by the Micropure® technique were well in accordance with 18F-NaF PET-CT scanning, with better sensitivity and specificity.