Regulatory T Cell in Stroke: A New Paradigm for Immune Regulation

Stroke is a common, debilitating trauma that has an incompletely elucidated pathophysiology and lacks an effective therapy. FoxP3+CD25+CD4+ regulatory T cells (Tregs) suppress a variety of normal physiological and pathological immune responses via several pathways, such as inhibitory cytokine secretion, direct cytolysis induction, and antigen-presenting cell functional modulation. FoxP3+CD25+CD4+ Tregs are involved in a variety of central nervous system diseases and injuries, including axonal injury, neurodegenerative diseases, and stroke. Specifically, FoxP3+CD25+CD4+ Tregs exert neuroprotective effects in acute experimental stroke models. These beneficial effects, however, are difficult to elucidate. In this review, we summarized evidence of FoxP3+CD25+CD4+ Tregs as potentially important immunomodulators in stroke pathogenesis and highlight further investigations for possible immunotherapeutic strategies by modulating the quantity and/or functional effects of FoxP3+CD25+CD4+ Tregs in stroke patients

A Tightly Coupled Bi-Level Coordination Framework for CAVs at Road Intersections

Since the traffic administration at road intersections determines the capacity bottleneck of modern transportation systems, intelligent cooperative coordination for connected autonomous vehicles (CAVs) has shown to be an effective solution. In this paper, we try to formulate a Bi-Level CAV intersection coordination framework, where coordinators from High and Low levels are tightly coupled. In the High-Level coordinator where vehicles from multiple roads are involved, we take various metrics including throughput, safety, fairness and comfort into consideration. Motivated by the time consuming space-time resource allocation framework in [1], we try to give a low complexity solution by transforming the complicated original problem into a sequential linear programming one. Based on the "feasible tunnels" (FT) generated from the High-Level coordinator, we then propose a rapid gradient-based trajectory optimization strategy in the Low-Level planner, to effectively avoid collisions beyond High-level considerations, such as the pedestrian or bicycles. Simulation results and laboratory experiments show that our proposed method outperforms existing strategies. Moreover, the most impressive advantage is that the proposed strategy can plan vehicle trajectory in milliseconds, which is promising in realworld deployments. A detailed description include the coordination framework and experiment demo could be found at the supplement materials, or online at https://youtu.be/MuhjhKfNIOg

Dominant patterns of winter Arctic surface wind variability

Dominant statistical patterns of winter Arctic surface wind (WASW) variability and their impacts on Arctic sea ice motion are investigated using the complex vector empirical orthogonal function (CVEOF) method. The results indicate that the leading CVEOF of Arctic surface wind variability, which accounts for 33% of the covariance, is characterized by two different and alternating spatial patterns (WASWP1 and WASWP2). Both WASWP1 and WASWP2 show strong interannual and decadal variations, superposed on their declining trends over past decades. Atmospheric circulation anomalies associated with WASWP1 and WASWP2 exhibit, respectively, equivalent barotropic and some baroclinic characteristics, differing from the Arctic dipole anomaly and the seesaw structure anomaly between the Barents Sea and the Beaufort Sea. On decadal time scales, the decline trend of WASWP2 can be attributed to persistent warming of sea surface temperature in the Greenland—Barents—Kara seas from autumn to winter, reflecting the effect of the Arctic warming. The second CVEOF, which accounts for 18% of the covariance, also contains two different spatial patterns (WASWP3 and WASWP4). Their time evolutions are significantly correlated with the North Atlantic Oscillation (NAO) index and the central Arctic Pattern, respectively, measured by the leading EOF of winter sea level pressure (SLP) north of 70°N. Thus, winter anomalous surface wind pattern associated with the NAO is not the most important surface wind pattern. WASWP3 and WASWP4 primarily reflect natural variability of winter surface wind and neither exhibits an apparent trend that differs from WASWP1 or WASWP2. These dominant surface wind patterns strongly influence Arctic sea ice motion and sea ice exchange between the western and eastern Arctic. Furthermore, the Fram Strait sea ice volume flux is only significantly correlated with WASWP3. The results demonstrate that surface and geostrophic winds are not interchangeable in terms of describing wind field variability over the Arctic Ocean. The results have important implications for understanding and investigating Arctic sea ice variations: Dominant patterns of Arctic surface wind variability, rather than simply whether there are the Arctic dipole anomaly and the Arctic Oscillation (or NAO), effectively affect the spatial distribution of Arctic sea ice anomalies

Anxiety Specific Response and Contribution of Active Hippocampal Neural Stem Cells to Chronic Pain Through Wnt/β-Catenin Signaling in Mice

Chronic pain usually results in persistent anxiety, which worsens the life quality of patients and complicates the treatment of pain. Hippocampus is one of the few brain regions in many mammalians species which harbors adult neural stem cells (NSCs), and plays a key role in the development and maintenance of chronic anxiety. Recent studies have suggested a potential involvement of hippocampal neurogenesis in modulating chronic pain. Whether and how hippocampal NSCs are involved in the pain-associated anxiety remains unclear. Here, we report that mice suffering persistent neuropathic pain showed a quick reduction of active NSCs in the ventral dentate gyrus (vDG), which was followed by the decrease of neurogenesis and appearance of anxiety. Wnt/β-catenin signaling, a key pathway in sustaining the active status of NSCs was suppressed in the vDG of mice suffering chronic pain. Depleting β-catenin by inducible Nestin-Cre significantly reduced the number of active NSCs and facilitated anxiety development, while expressing stabilized β-catenin amplified active NSCs and alleviated anxiety, indicating that Wnt activated NSCs is required for anxiety development under chronic pain. Treatment with Fluoxetine, the most widely used anxiolytic in clinic, significantly increased the proliferation of active NSCs and enhanced Wnt signaling. Interestingly, both β-catenin manipulation and Fluoxetine treatment had no significant effects on the pain thresholds. Therefore, our data demonstrated an anxiety-specific response and contribution of activated NSCs to chronic pain through Wnt/β-catenin signaling, which may be targeted for treating chronic pain- or other diseases-associated anxiety

MiR-650 represses high-risk non-metastatic colorectal cancer progression via inhibition of AKT2/GSK3β/E-cadherin pathway

Although 5-year survival rate of non-metastatic colorectal cancer (CRC) is high, about 10% of patients in stage I and II still develop into metastatic CRC and eventually die after resection. Currently, there is no effective biomarker for predicting the prognosis of non-metastatic CRC in clinical practice. In this study, we identified miR-650 as a biomarker for prognosis prediction. We observed that the expression of miR-650 in tumor tissues had a positive association with overall survival. MiR-650 inhibited cell growth and invasion in vitro and in vivo. Furthermore, miR-650 targeted AKT2 and repressed the activation of the AKT pathway (AKT2/GSK3β/E-cadherin). Thus it induced the translocation of E-cadherin and β-catenin in cancer cells. Our results highlight the potential of miR-650 as a prognostic prediction biomarker and therapeutic target in non-metastatic CRC via inhibition of the AKT2/GSK3β/E-cadherin pathway

Redistribution of the astrocyte phenotypes in the medial vestibular nuclei after unilateral labyrinthectomy

Astrocytes are highly heterogeneous and involved in different aspects of fundamental functions in the central nervous system (CNS). However, whether and how this heterogeneous population of cells reacts to the pathophysiological challenge is not well understood. To investigate the response status of astrocytes in the medial vestibular nucleus (MVN) after vestibular loss, we examined the subtypes of astrocytes in MVN using single-cell sequencing technology in a unilateral labyrinthectomy mouse model. We discovered four subtypes of astrocytes in the MVN with each displaying unique gene expression profiles. After unilateral labyrinthectomy, the proportion of the astrocytic subtypes and their transcriptional features on the ipsilateral side of the MVN differ significantly from those on the contralateral side. With new markers to detect and classify the subtypes of astrocytes in the MVN, our findings implicate potential roles of the adaptive changes of astrocyte subtypes in the early vestibular compensation following peripheral vestibular damage to reverse behavioral deficits