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Introduction The importance of oligodendrocytes and myelin in the central nervous system (CNS) is evidenced by the neuronal dysfunction and physical disability observed following their damage (1). Oligodendrocyte loss and [...], Impairment of oligodendrocytes and myelin contributes to neurological disorders including multiple sclerosis (MS), stroke, and Alzheimer's disease. Regeneration of myelin (remyelination) decreases the vulnerability of demyelinated axons, but this repair process commonly fails with disease progression. A contributor to inefficient remyelination is the altered extracellular matrix (ECM) in lesions, which remains to be better defined. We have identified fibulin-2 (FBLN2) as a highly upregulated ECM component in lesions of MS and stroke and in proteome databases of Alzheimer's disease and traumatic brain injury. Focusing on MS, the inhibitory role of FBLN2 was suggested in the experimental autoimmune encephalomyelitis (EAE) model, in which genetic FBLN2 deficiency improved behavioral recovery by promoting the maturation of oligodendrocytes and enhancing remyelination. Mechanistically, when oligodendrocyte progenitors were cultured in differentiation medium, FBLN2 impeded their maturation into oligodendrocytes by engaging the Notch pathway, leading to cell death. Adeno-associated virus deletion of FBLN2 in astrocytes improved oligodendrocyte numbers and functional recovery in EAE and generated new myelin profiles after lysolecithin-induced demyelination. Collectively, our findings implicate FBLN2 as a hitherto unrecognized injuryelevated ECM, and a therapeutic target, that impairs oligodendrocyte maturation and myelin repair.

Under the same geological conditions, the thickness and length of the reinforced strip, the slope ratio of the reinforced embankment, the modulus of elasticity of the fill and the reinforced strip, and the friction angle at the interface between the reinforcement and the soil, are the main design parameters that have an important influence on the stress, deformation, and stability of the encompassing reinforced soil embankment. To quickly and accurately determine the optimal design parameters for reinforced soil embankments with wrapped faces, ensuring minimal cost, while maintaining structural safety, we propose a design parameter prediction model based on a GA–BP neural network. This model evaluates parameters within their specified ranges, using maximum lateral displacement, maximum vertical displacement, maximum stress in the XZ direction, the maximum shear strain increment, and the safety factor, as assessment criteria. The primary objective is to minimize the overall cost of the embankment. A comparison with five machine learning algorithms shows that the model has high prediction accuracy, and the optimal design parameter combinations obtained from the optimization search can significantly reduce the cost of the embankment, while controlling the displacement and stability of the embankment. Therefore, the GA–BP network is suitable for predicting the optimal design parameters of reinforced soil embankments with wrapped faces. [ABSTRACT FROM AUTHOR]

A new bisabolane-type sesquiterpenoid, named (+)-8-dehydroxylaustrosene (1), along with ten known compounds, penicibisabolanes E (2) and G (3), (+)-austrosene (4), (S)-(+)-11-dehydrosydonic acid (5), sydonic acid (6), (7S,11S)-(+)-12-hydroxysydonic acid (7), (−)-(R)-hydroxysydonic acid (8), pseudaboydin A (9), (−)-(7 R,10R)-iso-10-hydroxysydowic acid (10), lumichrome (11), were identified from the fungus Aspergillus sydowii BTBU20213012 isolated from a marine sediment sample from the Western Pacific. The structures of the compounds were identified by HRESIMS and NMR data analysis. Compound 11 showed weak antimicrobial activity against Staphylococcus aureus with MIC value of 200 μg/mL. [ABSTRACT FROM AUTHOR]

Two new polyketide derivatives, penirubenones A and B (1 and 2), and two naturally rare amino-bis-tetrahydrofuran derivatives, penirubenamides A and B (3 and 4), together with nine known compounds (5–13) were isolated from the marine-derived fungus Penicillium rubens BTBU20213035. The structures were identified by HRESIMS and 1D and 2D NMR analyses, and their absolute configurations were determined by a comparison of experimental and calculated electronic circular dichroism (ECD) spectroscopy and 13C NMR data. We found that 6 exhibited antibacterial activity against Staphylococcus aureus, with an MIC value of 3.125 μg/mL, and 1 and 2 showed synergistic antifungal activity against Candida albicans at 12.5 and 50 μg/mL with 0.0625 μg/mL rapamycin. [ABSTRACT FROM AUTHOR]

This paper proposes a novel method based on continuum damage mechanics (CDM) and machine learning (ML) models to evaluate the vibration fatigue behavior of W1‐type railway fastener clips subjected to high‐frequency vibration. Firstly, static and fatigue tests are conducted on 60Si2Mn spring steel to acquire elastic modulus, tensile strength, and P‐S‐N curves. Subsequently, a CDM model is established, and numerical simulations are performed under various working conditions to obtain the fatigue characteristics of the clips. Finally, the ML model is trained using numerical simulation results, thereby establishing a mapping model between the working conditions and fatigue characteristics. The developed ML model demonstrates high accuracy in predicting the vibration fatigue life of the clips. Moreover, the Shapley Additive Explanations (SHAP) algorithm is employed to elucidate the ML model, revealing that the vibration frequency has a greater impact on the fatigue life of the clips compared to the vibration displacement. Highlights: A novel approach is developed for vibration fatigue assessment of fastener clip.The approach effectively combines the continuum damage model and ML (ANN) model.Static and fatigue tests of 60Si2Mn spring steel are conducted.Fatigue characteristic of clips subjected to high‐frequency vibration is studied. [ABSTRACT FROM AUTHOR]

Motor disturbances predominantly characterize hypoxic-ischemic encephalopathy (HIE). Among its intervention methods, environmental enrichment (EE) is strictly considered a form of sensory intervention. However, limited research uses EE as a single sensory input intervention to validate outcomes postintervention. A Sprague–Dawley rat model subjected to left common carotid artery ligation and exposure to oxygen-hypoxic conditions is used in this study. EE was achieved by enhancing the recreational and stress-relief items within the cage, increasing the duration of sunlight, colorful items exposure, and introducing background music. JZL184 (JZL) was administered as neuroprotective drugs. EE was performed 21 days postoperatively and the rats were randomly assigned to the standard environment and EE groups, the two groups were redivided into control, JZL, and vehicle injection subgroups. The Western blotting and behavior test indicated that EE and JZL injections were efficacious in promoting cognitive function in rats following HIE. In addition, the motor function performance in the EE-alone intervention group and the JZL-alone group after HIE was significantly improved compared with the control group. The combined EE and JZL intervention group exhibited even more pronounced improvements in these performances. EE may enhance motor function through sensory input different from the direct neuroprotective effect of pharmacological treatment. NEW & NOTEWORTHY: Rarely does literature assess motor function, even though it is common after hypoxia ischemic encephalopathy (HIE). Previously used environmental enrichment (EE) components have not been solely used as sensory inputs. Physical factors were minimized in our study to observe the effects of purely sensory inputs. [ABSTRACT FROM AUTHOR]