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This paper investigates the navigation problem of autonomous vehicles based on reinforcement learning (RL) with both stability and smoothness guarantees. By introducing a data-based Lyapunov function, the stability criterion in mean cost is obtained, where the Lyapunov function has a property of fast descending. Then, an off-policy RL algorithm is proposed to train safe policies, in which a more strict constraint is exerted in the framework of model-free RL to ensure the fast convergence of policy generation, in contrast with the existing RL merely with stability guarantee. In addition, by simultaneously introducing constraints on action increments and action distribution variations, the difference between the adjacent actions is effectively alleviated to ensure the smoothness of the obtained policy, instead of only seeking the similarity of the distributions of adjacent actions as commonly done in the past literature. A navigation task of a ground differentially driven mobile vehicle in simulations is adopted to demonstrate the superiority of the proposed algorithm on the fast stability and smoothness.

Hyperuricemia (HUA) is a widespread metabolic disease marked by an elevated level of uric acid, and is a risk factor for premature death. The protective effect of corn silk flavonoids (CSF) against HUA and its potential mechanisms were explored. Five important apoptosis and inflammation-related signaling pathways were identified by network pharmacological analysis. The CSF exhibited significant uric acid (UA)-lowering activity in vitroby decreasing xanthine oxidase (XOD) and increasing hypoxanthine–guanine phosphoribosyl transferase levels. In a potassium oxonate-induced HUA in vivo, CSF treatment effectively inhibited XOD activity and promoted UA excretion. Furthermore, it decreased the levels of TNF-α and IL-6 and restored pathological damage. In summary, CSF is a functional food component to improve HUA by reducing inflammation and apoptosis through the down-regulating PI3K/AKT/NF-κB pathway.

This paper is concerned with the issue of path optimization for manipulators in multi-obstacle environments. Aimed at overcoming the deficiencies of the sampling-based path planning algorithm with high path curvature and low safety margin, a path optimization method, named NA-OR, is proposed for manipulators, where the NA (node attraction) and OR (obstacle repulsion) functions are developed to refine the path by iterations. In the iterations of path optimization, the node attraction function is designed to pull the path nodes toward the center of their neighbor nodes, thereby reducing the path curvature and improving the smoothness. Also, the obstacle repulsion function is developed to push the path nodes out of the potentially unsafe region by generating a repulsive torque on the path nodes, thus improving the safety margin of the motion. By introducing the effect of NA-OR, the optimized path has a significant improvement in path curvature and safety margin compared with the initial path planned by Bi-RRT, which meaningfully enhances the operation ability of manipulators for the applications that give a strong emphasis on security. Experimental results on a 6-DOF manipulator in 4 scenarios demonstrate the effectiveness and superiority of the proposed method in terms of the path cost, safety margin, and path smoothness.

Neurodegeneration occurring in multiple sclerosis (MS) contributes to the progression of disability. It is therefore important to identify and neutralize the mechanisms that promote neurodegeneration in MS. Here, we report that oxidized phosphatidylcholines (OxPCs) found in MS lesions, previously identified as end-product markers of oxidative stress, are potent drivers of neurodegeneration. Cultured neurons and oligodendrocytes were killed by OxPCs, and this was ameliorated by microglia. After OxPC injection, mouse spinal cords developed focal demyelinating lesions with prominent axonal loss. The depletion of microglia that accumulated in OxPC lesions exacerbated neurodegeneration. Single-cell RNA sequencing of lesioned spinal cords identified unique subsets of TREM2highmouse microglia responding to OxPC deposition. TREM2 was detected in human MS lesions, and TREM2−/−mice exhibited worsened OxPC lesions. These results identify OxPCs as potent neurotoxins and suggest that enhancing microglia-mediated OxPC clearance via TREM2 could help prevent neurodegeneration in MS.

Focal fibrocartilaginous dysplasia (FFCD) of the distal femur is a rare disorder that results in a varus or valgus of knee. Due to the small number of cases and unconfirmed natural history of the disease, treatment methods remain variable. This study aimed to determine a strategy to successfully manage distal femoral FFCD. Nine case of femoral FFCD treated in our department between 2008 and 2018, together with 22 cases from literature, were retrospectively reviewed. Tibiofemoral anatomical axis angle (TFA) was used to evaluate and follow the deformities. Treatment methods and outcome were analyzed. Five methods were used to manage the disease: osteotomy with tether release in 14 cases with mean TFA of 29°; simple tether release in eight cases with mean TFA of 31°; guide growth without tether release in 3 case with mean TFA of 27°; guide growth with tether release in 3 case with mean TFA of 27°; and observation in three cases with mean TFA of 23°.Deformity was resolved in all 31 patients. The analysis of the 31 cases in the literature and our experience suggests that femoral FFCD can be successfully managed by simple tether release and curettage. Osteotomy can be avoided. In case of mild deformity (TFA < 25°), it is reasonable to follow-up till 2–3 years of age; if no progress occurs, spontaneous resolution can be expected.

•XIST may serve as a prognostic biomarker for cholangiocarcinoma.•Overexpression of XIST inhibited tumor progression by targeting miR-126-3p.•XIST has a carcinogenic role in cholangiocarcinoma.

In this study, SHECN (Ser-His-Glu-Cys-Asn) and SHCMN (Ser-His-Cys-Met-Asn) soybean peptides were used as the research objects to investigate their antioxidant activities and XO (xanthine oxidase) activity reduction effects. The results show that SHECN and SHCMN have strong antioxidant activities, and at the same time protect the oxidative stress damage caused by HUA (hyperuricemia). They can quench XO, change the secondary structure of XO, and reduce its activity, which leads to the reduction of UA (uric acid) levels. Molecular docking demonstrated soybean peptides could bind to XO target proteins, respectively. In this study, SHECN and SHCMN were obtained from soybean peptides. Based on the data, soy peptides may be an attractive natural ingredient for the development of novel functional foods that inhibit XO activity.

Oxidized phosphatidylcholine (OxPC) found in multiple sclerosis brain lesions mediates neurodegeneration. Microglia are prominent responders to the OxPC insult, and thus, studying their protective or noxious functions is important to help halt neurodegeneration. Here, we present protocols including cell isolation and culture, animal surgeries, as well as tissue processing and isolation to study the microglia response to OxPC-mediated neurodegeneration in vitroand in vivo.

The process of autophagy is conserved among all eukaryotes from yeast to humans and is mainly responsible for bulk degradation of cellular contents and nutrient recycling during starvation. Autophagy has been suggested to play a role in the pathogenesis of the opportunistic human fungal pathogen Cryptococcus neoformans, potentially through a contribution to the export of virulence factors.