Membrane fluidity regulates high shear stress-induced FAK activation at different subcellular compartments

Focal adhesion kinase(FAK)plays a vital role in mediating the adaptability of tumor cells under mechanical stimuli.Previous studies revealed that FAK can locate to different cell compartments,and its regulation is highly dependent on its subcellular localization.However,the local FAK activities and its regulation mechanism in different cell compartments of tumor cells in response to fluid shear stress are still unclear.In this study,5 dyn/cm^(2) and 20 dyn/cm^(2) of shear stress was applied to HeLa cells for 30 min.The activities of FAK targeting different subcellular compartments(lipids rafts,non-rafts,focal adhesions and cytoplasm)were investigated with fluorescence resonance energy transfer(FRET)technology.Results showed that the activity of FAK in response to high shear stress at focal adhesion sites was lower than that of other three areas,while no difference among four areas was observed in response to low shear stress.Furthermore,high shear stress-induced distinct FAK activation at different compartments was inhibited by decreasing membrane fluidity,but Src inhibition prevented high shear stress-induced FAK activation only in the cytoplasm.This study revealed the spatiotemporal characteristics of FAK under the different magnitude of shear stress,which provides a deeper understanding of mechanotransduction in tumor cells.

Tissue induction, the relationship between biomaterial’s microenvironment and mesenchymal stem cell differentiation

Mesenchymal stem cells (MSCs) have been recognized as the best candidate for tissue engineering, while the mechanism of biomaterial-induced MSCs differentiation is not well understood. Most of research has been focused on chemical signaling of biomaterial in the past, but a variety of non-chemical signals were also proved to play essential roles in cellular behaviors. In this paper, we reviewed the current reports about the effects of different kinds of biomaterial signals on MSCs differentiation.

神经递质的可视化荧光检测技术研究进展

神经递质是神经系统中至关重要的组成部分,神经递质释放的时间和空间变化是神经网络中信息处理的核心,可视化监测神经递质的生物传感器是探究各类生理和病理活动的重要工具。文中综述了近年来具有较高时间和空间分辨率的监测神经递质时空分布变化技术的研究进展,介绍了对谷氨酸、多巴胺、γ-氨基丁酸和乙酰胆碱这4类重要的神经递质的检测方法,并归纳总结了各类检测方法的基本原理和优缺点,为设计具有高时空分辨率的神经递质传感器提供一个较为系统的参考。

Endovascular therapy for Acute ischemic Stroke Trial (EAST): study protocol for a prospective, multicentre control trial in China

Background and purpose:5 recent trials have shown the benefit of endovascular treatment for acute ischaemic stroke(AIS)due to large vessel occlusion of the anterior circulation.This study aims to evaluate the safety and efficacy of Solitaire thrombectomy in patients with moderate-to-severe stroke in the Chinese population,which has a high prevalence of intracranial atherosclerosis.Methods and analysis:This multicentre prospective control study will involve 17 stroke centres in China,and plans to recruit 150 patients in the intervention group,and 150 patients in the medical group,in which patients meet enrolment criteria but refuse intervention.Patients with AIS due to large vessel occlusion indicated for treatment with Solitaire stent retriever within 12 hours of symptom onset,and who meet the inclusion and exclusion criteria,will be enrolled in this study.The primary efficacy endpoint is functional independence as defined by a modified Rankin Scale(mRS)score≤2 at 90 days or by functional improvement as defined by mRS,using shift analysis.The procedural efficacy endpoint is arterial recanalisation of the occluded target vessel measured by a modified Thrombolysis in Cerebral Infarction(mTICI)score equal or superior to 2b right following the use of the study device.The primary safety endpoint is symptomatic intracranial haemorrhage(sICH)within 24±3 hours postprocedure.Ethics and dissemination:The protocol was approved by the Ethics Committee at the coordinating centre and by the local Institutional Review Board of each participating centre.Trial registration number:NCT02350283.

ROS-responsive biomimetic nanoparticles for potential application in targeted anti-atherosclerosis

The development of nanomedicines provides new opportunities for the treatment of atherosclerosis(AS)due to their great advantages such as the improved drug solubility,enhanced bioavailability and reduced side effects.Despite these advantages,nanomedicines are still facing some challenges.The problems remain in the short circulation life,lack of specific targeting and poor drug release controllability.In order to overcome the shortages of conventional nanomedicines,the combination of biomimetic strategy with smart nanoagents has been proposed.In light with the high reactive oxygen species(ROS)level in AS microenvironment and the fact that macrophages play a critical role in the pathogenesis of AS,we fabricated ROS-responsive biomimetic nanoparticles(NPs),which camouflaged macrophage membrane(MM)on ROS-responsive NPs loaded with rapamycin(RNPs)for potential application in AS therapy.The resulting ROSresponsive biomimetic NPs(MM/RNPs)exhibited favorable hydrodynamic size with negative surface charge,retained the functional proteins from MM,and showed ROS-responsive drug release.Because of the biomimetic camouflaging on surface,MM/RNPs could effectively escape from macrophages uptake and target to inflammatory endothelial cells.Meanwhile,MM/RNPs could inhibit the proliferation of macrophages and smooth muscle cells in vitro.Furthermore,the MM-coated NPs were found to be nontoxic in both cytotoxicity assay and in vivo toxicity evaluation.Consequently,these results demonstrated that MM/RNPs could be a potential candidate of drug delivery system for safe and effective anti-AS applications.

Impairment of cognition and sleep after acute ischaemic stroke or transient ischaemic attack in Chinese patients: design, rationale and baseline patient characteristics of a nationwide multicentre prospective registry

background and aim Cognitive impairment and sleep disorder are both common poststroke conditions and are closely related to the prognosis of patients who had a stroke.The Impairment of CognitiON and Sleep after acute ischemic stroke or transient ischemic attack in Chinese patients(ICONS)study is a nationwide multicentre prospective registry to investigate the occurrence and associated factors of cognitive impairment and sleep disorder after acute ischaemic stroke(AIS)or transient ischaemic attack(TIA).Methods Consecutive AIS or TIA in-hospital patients within 7 days after onset were enrolled from 40 participating sites in China.Comprehensive baseline clinical and imaging data were collected prospectively.Blood and urine samples were also collected on admission and follow-up visits.Patients were interviewed face to face for cognition and sleep related outcomes at 2 weeks,3,6 and 12 months after AIS/TIA and followed up for clinical outcomes by telephone annually over 5 years.results Between August 2015 and January 2018,a total of 2625 patients were enrolled.92.65% patients had AIS and 7.35% patients had TIA.Overall,the average age was 61.04 years,and 72.38% patients were male.Median National Institutes of Health Stroke Scale score was 3 in AIS patients.Conclusions The ICONS study is a large-scale nationwide prospective registry to investigate occurrence and the longitudinal changes of cognitive impairment and sleep disorder after AIS or TIA.Data from this registry may also provide opportunity to evaluate associated factors of cognitive impairment or sleep disorder after AIS or TIA and their impact on clinical outcome.

Intelligent deformation of biomedical polyurethane

Polyurethane is a general term for a class of polymerscontaining a carbamate group(-NHCOO-)in its mainchain structure,including thermoplastic elastomers,flexi-ble and rigid foams,and other species[1-2].The existenceof thermodynamically incompatible soft segments and hardsegments in the structure of polyurethane can causemicrophase separation,which gives polyurethane somesuperior characteristics.Its performance can be adjusted byredesigning the proportion and the structure of soft andhard segments[3-5].

Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction (STRATEGY): protocol for a multicentre, randomised controlled trial

Background Perforating artery territorial infarction(PAI)caused by branch atheromatous disease(BAD)is prone to recurrence and early progression without an effective and well-documented antiplatelet treatment regimen.Tirofiban,an adjunctive antiplatelet agent,has shown great potential to treat acute ischaemic stroke.However,whether the combination of tirofiban and aspirin can improve the prognosis of PAI remains unclear.Aim To explore an effective and safe antiplatelet regimen for reducing the risk of recurrence and early neurological deterioration(END)in PAI caused by BAD by comparing the tirofiban and aspirin combination with placebo and aspirin combination.Methods Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction(STRATEGY)trial is an ongoing multicentre,randomised,placebo-controlled trial in China.Eligible patients shall be randomly assigned to receive standard aspirin with tirofiban or placebo on the first day and standard aspirin from days 2 to 90.The primary endpoint is a new stroke or END within 90 days.The primary safety endpoint is severe or moderate bleeding within 90 days.Discussion The STRATEGY trial will assess whether tirofiban combined with aspirin is effective and safe in preventing recurrence and END in patients with PAI.Trial registration number NCT05310968.