Induced pluripotent stem cell model revealed impaired neurovascular interaction in genetic small vessel disease Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

IntroductionCerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common genetic small vessel disease caused by variants in the NOTCH3 gene. Patients with CADASIL experience recurrent strokes, developing into cognitive defect and vascular dementia. CADASIL is a late-onset vascular condition, but migraine and brain MRI lesions appear in CADASIL patients as early as their teens and twenties, suggesting an abnormal neurovascular interaction at the neurovascular unit (NVU) where microvessels meet the brain parenchyma.MethodsTo understand the molecular mechanisms of CADASIL, we established induced pluripotent stem cell (iPSC) models from CADASIL patients and differentiated the iPSCs into the major NVU cell types including brain microvascular endothelial-like cells (BMECs), vascular mural cells (MCs), astrocytes and cortical projection neurons. We then built an in vitro NVU model by co-culturing different neurovascular cell types in Transwells and evaluated the blood brain barrier (BBB) function by measuring transendothelial electrical resistance (TEER).ResultsResults showed that, while the wild-type MCs, astrocytes and neurons could all independently and significantly enhance TEER of the iPSC-BMECs, such capability of MCs from iPSCs of CADASIL patients was significantly impaired. Additionally, the barrier function of the BMECs from CADASIL iPSCs was significantly decreased, accompanied with disorganized tight junctions in iPSC-BMECs, which could not be rescued by the wild-type MCs or sufficiently rescued by the wild-type astrocytes and neurons.DiscussionOur findings provide new insight into early disease pathologies on the neurovascular interaction and BBB function at the molecular and cellular levels for CADASIL, which helps inform future therapeutic development

An optimal bidding and scheduling method for load service entities considering demand response uncertainty

With the rapid development of demand-side management technologies, load serving entities (LSEs) may offer demand response (DR) programs to improve the flexibility of power system operation. Reliable load aggregation is critical for LSEs to improve profits in electricity markets. Due to the uncertainty, the actual aggregated response of loads obtained by conventional aggregation methods can experience significant deviations from the bidding value, making it difficult for LSEs to develop an optimal bidding and scheduling strategy. In this paper, a bi-level scheduling model is proposed to maximize the net revenue of the LSE from optimal DR bidding and energy storage systems ESS scheduling by considering the impacts of the uncertainty of demand response. An online learning method is adopted to improve aggregation reliability. Additionally, the net profit for LSEs can be raised by strategically switching ESS between two modes, namely, energy arbitrage and deviation mitigation. With Karush–Kuhn–Tucker (KKT) optimality condition-based decoupling and piecewise linearization applied, this bi-level optimization model can be reformulated and converted into a mixed-integer linear programming (MILP) problem. The effectiveness and advantages of the proposed method are verified in a modified IEEE RTS-24 bus system.publishedVersionPeer reviewe

Well-Placed Acetabular Component Oriented Outside the Safe Zone During Weight-Bearing Daily Activities

Background: A comprehensive and thorough understanding of functional acetabular component orientation is essential for optimizing the clinical outcome after total hip arthroplasty (THA). This study aimed to quantify the functional acetabular anteversion and inclination of unilateral THA patients during walking and static standing and to determine whether the functional acetabular orientation falls within the Lewinnek safe zone.Methods: Seventeen patients with unilateral THA received a CT scan and dual fluoroscopic imaging during level walking and static standing to evaluate in vivo hip kinematics. The pelvic functional coordinate system of the 3D CT-based computer model was defined by the line of gravity and anterior pelvic plane (APP) to measure functional acetabular anteversion and inclination in different postures. The Lewinnek safe zone was used to determine the acetabular malposition during functional activities.Results: The THA side demonstrated an average of 10.1° (± 9.6°, range –7.5° to 29.9°) larger functional anteversion and 16.0° (± 9.2°, range –7.2° to 29.9°) smaller inclination than native hips during level walking. Functional acetabular anteversion in the THA side during level walking and static standing was significantly larger than anatomical measurements (p < 0.05). Acetabular orientation of most well-placed THA components anatomically in the Lewinnek safe zone fell outside the safe zone during more than half of the gait cycle and static standing.Conclusion: The current study revealed that an anatomically well-placed acetabular cup does not guarantee a well-functional orientation during daily activities. The in vivo mechanical performance and loading conditions of the THA component during other weight-bearing activities should be investigated in further studies

MicroRNA-7 inhibits epithelial-to-mesenchymal transition and metastasis of breast cancer cells via targeting FAK expression

10.1371/journal.pone.0041523PLoS ONE78

Singlemode-Multimode-Singlemode Optical Fiber Sensor for Accurate Blood Pressure Monitoring

A dual-channel single-mode-multi-mode-single-mode (SMS) fiber optic sensor encapsulated by polydimethylsiloxane (PDMS) was proposed for the first time, for the simultaneous monitoring of the brachial and radial arteries for accurate blood pressure prediction. With the help of the machine learning algorithm Support Vector Regression (SVR), the SMS fiber sensor can continuously and accurately monitor the systolic and diastolic blood pressure. Commercial sphygmomanometers are used to calibrate the accuracy of blood pressure measurement. Compared with the single-channel system, this system can extract more pulse wave features for blood pressure prediction, such as radial artery transit time (RPTT), brachial artery transit time (BPTT), and the transit time difference between the radial artery and the brachial artery (DBRPTT). The results show that the performance of dual-channel blood pressure monitoring is more accurate than that of single-channel blood pressure monitoring in terms of the absolute value of the correlation coefficient (R) and the average value of the difference between SBP and DBP. In addition, both the single-channel and dual-channel blood pressure monitoring are in line with the Association for the Advancement of Medical Devices (AAMI), but the average deviation (DM, 0.06 mmHg) and standard deviation (SD, 1.54 mmHg) of dual-channel blood pressure monitoring are more accurate. The blood pressure monitoring system has the characteristics of low cost, high sensitivity, non-invasive and capability for remote real time monitoring, which can provide effective solution for intelligent health monitoring in the era of artificial intelligence in the future

Perforating scleral vessels adjacent to myopic choroidal neovascularization achieved a poor outcome after intravitreal anti-VEGF therapy

BackgroundThis study aimed to summarize the features of perforating scleral vessels (PSVs) in patients with myopic choroidal neovascularization (CNV) (mCNV) using optical coherence tomography angiography (OCTA) and to identify the associations with the response after intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy.MethodsA consecutive series of naïve patients who had mCNV and received intravitreal anti-VEGF therapy with a follow-up duration of 12 months or more were enrolled. The prevalence, location, and branches of PSVs were analyzed. Projection-resolved OCTA (PR-OCTA) was used to analyze the neovascular signals between CNV and PSVs. Best corrected visual acuity (BCVA) and central macular thickness (CMT) were measured. The proportion of CMT change relative to baseline was used to assess therapeutic response.ResultsA total of 44 eyes from 42 patients with mCNV were enrolled. PSVs were identified in 41 out of 44 eyes. Branches were identified in the PSVs of 24 eyes (57.14%), and 20 eyes did not have PSV branches (47.62%). In eight eyes (18.18%), PSVs were adjacent to mCNV, and in 36 eyes (81.82%), PSVs were not adjacent to mCNV. After anti-VEGF therapy for mCNV, BCVA increased (F = 6.119, p < 0.001) and CMT decreased (F = 7.664, p < 0.001). In the eyes where PSVs were adjacent to mCNV, BCVA improvements (F = 7.649, p = 0.009) were poor, and changes in CMT were small.ConclusionThe eyes with PSVs adjacent to mCNV showed poor therapeutic responses after intravitreal anti-VEGF therapy