The Importance of Platelets Response during Antiplatelet Treatment after Ischemic Stroke—Between Benefit and Risk: A Systematic Review

Ischemic stroke is a disease related to abnormal blood flow that leads to brain dysfunction. The early and late phases of the disease are distinguished. A distinction is made between the early and late stages of the disease, and the best effect in treating an ischemic stroke is usually achieved within the first hours after the onset of symptoms. This review looked at studies platelet activity monitoring studies to determine the risks and benefits of various approaches including antiplatelet therapy. A study was conducted on recently published literature based on PRISMA. This review includes 32 research articles directly addressing the importance of monitoring platelet function during antiplatelet therapy (dual or monotherapy) after ischemic stroke. In patients with transient ischemic attack or ischemic stroke, antiplatelet therapy can reduce the risk of stroke by 11–15%, assuming that patients respond well. Secondary prevention results are dependent on platelet reactivity, meaning that patients do not respond equally to antiplatelet therapy. It is very important that aspirin-resistant patients can benefit from the use of dual antiplatelet therapy. The individualized approach to secondary stroke prevention is to administer the most appropriate drug at the correct dose and apply the optimal therapeutic procedure to the individual patient.     

Disassembly and Mislocalization of AQP4 in Incipient Scar Formation after Experimental Stroke

There is an urgent need to better understand the mechanisms involved in scar formation in the brain. It is well known that astrocytes are critically engaged in this process. Here, we analyze incipient scar formation one week after a discrete ischemic insult to the cerebral cortex. We show that the infarct border zone is characterized by pronounced changes in the organization and subcellular localization of the major astrocytic protein AQP4. Specifically, there is a loss of AQP4 from astrocytic endfoot membranes that anchor astrocytes to pericapillary basal laminae and a disassembly of the supramolecular AQP4 complexes that normally abound in these membranes. This disassembly may be mechanistically coupled to a downregulation of the newly discovered AQP4 isoform AQP4ex. AQP4 has adhesive properties and is assumed to facilitate astrocyte mobility by permitting rapid volume changes at the leading edges of migrating astrocytes. Thus, the present findings provide new insight in the molecular basis of incipient scar formation.     

Blood–Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke

Globally, stroke is a leading cause of death and long-term disability. Over the past decades, several efforts have attempted to discover new drugs or repurpose existing therapeutics to promote post-stroke neurological recovery. Preclinical stroke studies have reported successes in identifying novel neuroprotective agents; however, none of these compounds have advanced beyond a phase III clinical trial. One reason for these failures is the lack of consideration of blood–brain barrier (BBB) transport mechanisms that can enable these drugs to achieve efficacious concentrations in ischemic brain tissue. Despite the knowledge that drugs with neuroprotective properties (i.e., statins, memantine, metformin) are substrates for endogenous BBB transporters, preclinical stroke research has not extensively studied the role of transporters in central nervous system (CNS) drug delivery. Here, we review current knowledge on specific BBB uptake transporters (i.e., organic anion transporting polypeptides (OATPs in humans; Oatps in rodents); organic cation transporters (OCTs in humans; Octs in rodents) that can be targeted for improved neuroprotective drug delivery. Additionally, we provide state-of-the-art perspectives on how transporter pharmacology can be integrated into preclinical stroke research. Specifically, we discuss the utility of in vivo stroke models to transporter studies and considerations (i.e., species selection, co-morbid conditions) that will optimize the translational success of stroke pharmacotherapeutic experiments.     

角行程阀门电液执行器传动结构的分析

介绍了角行程电液执行器的几种常见传动结构,分析了各种结构的力矩输出特性及与阀门配套的特点.     

Insulin-like Growth Factor 1 Promotes Cell Proliferation by Downregulation of G-Protein-Coupled Receptor 17 Expression via PI3K/Akt/FoxO1 Signaling in SK-N-SH Cells

Insulin-like growth factor 1 (IGF-1) not only regulates neuronal function and development but also is neuroprotective in the setting of acute ischemic stroke. G-protein-coupled receptor 17 (GPR17) expression in brain tissue serves as an indicator of brain damage. As whether IGF-1 regulates GPR17 expression remains unknown, the aim of this study is to investigate how IGF-1 regulates GPR17 expression in vitro. Human neuroblastoma SK-N-SH cells were used. Lentivirus-mediated short hairpin RNA (shRNA) was constructed to mediate the silencing of FoxO1, while adenoviral vectors were used for its overexpression. Verification of the relevant signaling cascade was performed using a FoxO1 inhibitor (AS1842856), a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), and a GPR17 antagonist (cangrelor). Cell proliferation was analyzed using EdU staining; immunofluorescence staining was used to detect the expression and subcellular localization of FoxO1. Chromatin immunoprecipitation was used to analyze the binding of FoxO1 to the GPR17 promoter in SK-N-SH cells. The expression of FoxO1, GPR17, and protein kinase B (also known as Akt) mRNA and protein as well as the levels of FoxO1 and Akt phosphorylation were investigated in this study. IGF-1 was found to downregulate FoxO1 and GPR17 expression in SK-N-SH cells while promoting cell viability and proliferation. Inhibition of FoxO1 and antagonism of GPR17 were found to play a role similar to that of IGF-1. Silencing of FoxO1 by lentivirus-mediated shRNA resulted in the downregulation of FoxO1 and GPR17 expression. The overexpression of FoxO1 via adenoviral vectors resulted in the upregulation of FoxO1 and GPR17 expression. Blocking of PI3K signaling by LY294002 inhibited the effect of IGF-1 on GPR17 suppression. Results from chromatin immunoprecipitation revealed that IGF-1 promotes FoxO1 nuclear export and reduces FoxO1 binding to the GPR17 promoter in SK-N-SH cells. Here, we conclude that IGF-1 enhances cell viability and proliferation in SK-N-SH cells via the promotion of FoxO1 nuclear export and reduction of FoxO1 binding to the GPR17 promoter via PI3K/Akt signaling. Our findings suggest that the enhancement of IGF-1 signaling to antagonize GPR17 serves as a potential therapeutic strategy in the management of acute ischemic stroke.     

基于光谱分类模型的保险杠物证无损研究

采用中红外光谱结合化学计量学的方法对车用保险杠碎片进行鉴别,分别对52个车用保险杠碎片样本的全波段光谱数据、指纹区光谱数据和主成分分析降维后的光谱数据建立Fisher判别分析和K近邻算法2种分类模型,并对分类结果进行比较。结果表明,主成分分析提取特征变量后构建的分类模型,分类的准确率更高,对聚丙烯（PP）、PP/滑石粉、PP/滑石粉/碳酸钙（CaCO₃）3种类型的样本分类准确率达到92.3 %,对PP/滑石粉类型中的10种品牌样本分类准确率达到88.9 %,分类结果理想;在构建的2种分类模型中,Fisher判别分析模型的分类率远高于K近邻算法模型,分析认为K近邻算法模型受到样本不均衡的影响;中红外光谱结合化学计量学可以实现对车用保险杠碎片的准确区分,且满足快速、无损的检验要求。     

The Clinical Significance of Transfer RNAs Present in Extracellular Vesicles

Extracellular vesicles (EVs) are important for intercellular signalling in multi-cellular organisms. However, the role of mature transfer RNAs (tRNAs) and tRNA fragments in EVs has yet to be characterised. This systematic review aimed to identify up-to-date literature on tRNAs present within human EVs and explores their potential clinical significance in health and disease. A comprehensive and systematic literature search was performed, and the study was conducted in accordance with PRISMA guidelines. Electronic databases MEDLINE and EMBASE were searched up until 1 January 2022. From 685 papers, 60 studies were identified for analysis. The majority of papers reviewed focussed on the role of EV tRNAs in cancers (31.7%), with numerous other conditions represented. Blood and cell lines were the most common EV sources, representing 85.9% of protocols used. EV isolation methods included most known methods, precipitation being the most common (49.3%). The proportion of EV tRNAs was highly variable, ranging between 0.04% to >95% depending on tissue source. EV tRNAs are present in a multitude of sources and show promise as disease markers in breast cancer, gastrointestinal cancers, and other diseases. EV tRNA research is an emerging field, with increasing numbers of papers highlighting novel methodologies for tRNA and tRNA fragment discovery.     

Enhancing Post-Stroke Rehabilitation and Preventing Exo-Focal Dopaminergic Degeneration in Rats—A Role for Substance P

Dopaminergic signaling is a prerequisite for motor learning. Delayed degeneration of dopaminergic neurons after stroke is linked to motor learning deficits impairing motor rehabilitation. This study investigates safety and efficacy of substance P (SP) treatment on post-stroke rehabilitation, as this neuropeptide combines neuroprotective and plasticity-promoting properties. Male Sprague Dawley rats received a photothrombotic stroke within the primary motor cortex (M1) after which a previously acquired skilled reaching task was rehabilitated. Rats were treated with intraperitoneal saline (control group, n = 7) or SP-injections (250 µg/kg) 30 min before (SP-pre; n = 7) or 16 h (SP-post; n = 6) after rehabilitation training. Dopaminergic neurodegeneration, microglial activation and substance P-immunoreactivity (IR) were analyzed immunohistochemically. Systemic SP significantly facilitated motor rehabilitation. This effect was more pronounced in SP-pre compared to SP-post animals. SP prevented dopaminergic cell loss after stroke, particularly in the SP-pre condition. Despite its proinflammatory propensity, SP administration did not increase stroke volumes, post-stroke deficits or activation of microglia in the midbrain. Finally, SP administration prevented ipsilesional hypertrophy of striatal SPergic innervation, particularly in the SP-post condition. Mechanistically, SP-pre likely involved plasticity-promoting effects in the early phase of rehabilitation, whereas preservation of dopaminergic signaling may have ameliorated rehabilitative success in both SP groups during later stages of training. Our results demonstrate the facilitating effect of SP treatment on motor rehabilitation after stroke, especially if administered prior to training. SP furthermore prevented delayed dopaminergic degeneration and preserved physiological endogenous SPergic innervation.     

牛免疫球蛋白G的体外人源唾液酸化及Fc片段的制备

建立将牛免疫球蛋白G (bovine immunoglobulin G,bIgG)糖链末端N-羟乙酰神经氨酸酶切并连接人源N-乙酰神经氨酸(N-acetylneuraminic acid,Neu5Ac)的方法,在实现bIgG转化为人源IgG (human IgG,hIgG)的基础上,研究hIgG可结晶(Fc)片段的制备...     

炸药驱动预制破片轴向抛掷速度规律研究

为解决爆轰产物对轴向预制破片的作用压力从柱状装药中心沿径向逐渐降低,从而导致轴向预制破片抛掷速度沿径向逐渐变小的问题,研究了柱状装药长径比与装药壳体厚度等装药结构参数对轴向预制破片抛掷速度沿径向分布规律的影响,针对某种轴向前置预制破片战斗部,进行了破片轴向抛掷速度沿径向分布规律的试验.结果表明,装药长径比以及装药壳体等装药结构参数对轴向预制破片抛掷速度影响较大,通过装药尺寸、壳体厚度等参数匹配,可以调整轴向预制破片的抛掷速度.