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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., 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 [...]

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]

Clarifying the mechanical characteristics of gas hydrate-bearing sediments (GHBS) from a mechanical perspective is crucial for ensuring the long-term, safe, and efficient extraction of natural gas hydrates. In this study, seabed soft clay from the northern South China Sea was utilized to prepare clayey silt samples, aligning with gradation curves related to hydrate extraction projects in the Shenhu area of the South China Sea. Utilizing the high-pressure low-temperature hydrate triaxial testing system (ETAS), twelve sets of triaxial shear tests were conducted. The results highlight that increases in hydrate saturation and confining pressure significantly enhance GHBS' strength and stiffness, with more pronounced volume expansion observed during shearing. These tests have elucidated the mechanical responses of GHBS. Subsequently, empirical formulas were developed to characterize their properties under varying conditions. Additionally, based on the experimental data, the micro-mechanisms of GHBS were analyzed, suggesting that hydrates notably contribute to the filling and cementing effects in GHBS, with these effects varying with changes in hydrate saturation and confining pressure. This study contributes to a deeper understanding of the fundamental mechanical properties of GHBS. [ABSTRACT FROM AUTHOR]

Context Adrenal venous sampling (AVS) is considered the gold standard for differentiating unilateral and bilateral forms of primary aldosteronism. Currently, almost all AVS procedures are performed via femoral vein access. Objective The aim of this study was to evaluate the success rate and safety of AVS via an antecubital approach. Methods In a retrospective multicenter study involving 7 Chinese medical centers, patients with primary aldosteronism who underwent AVS via an antecubital approach between January 2012 and December 2018 were analyzed. Successful sampling was determined by a selectivity index (cortisol in the adrenal vein/cortisol in inferior vena cava) greater than 2. Results A total of 1226 participants (mean age, 47.1 years; 57.9% male) were included. The puncture site was right and left antecubital vein in 1211 (98.8%), and 15 (1.2%) patients. The access of 6 patients (0.5%) was changed to right femoral vein due to the failure of antecubital vein cannulation or anatomic variation of adrenal vein. The success rate of bilateral, right, and left sampling was 91.5%, 94.9%, and 95.1%, respectively. The success rate of bilateral, right, and left sampling increased from 82.9%, 87.1%, and 88.6% during the initial 70 cases (total of initial 10 cases at each center) to 92.0% (P =.012), 95.3% (P =.008), and 95.5% (P =.018) with subsequent cases. Adrenal vein rupture occurred in 5 patients (0.41%), with no sequelae. Conclusion This multicenter study demonstrates that AVS via an antecubital approach is safe and feasible, with a high rate of successful sampling, which may be an alternative to the femoral vein access method. [ABSTRACT FROM AUTHOR]

High blood concentrations of nonesterified fatty acids (NEFA) during ketosis enhance uptake by the mammary gland and impair autophagy while causing oxidative stress. Caveolin 1 (CAV1) is closely related to autophagy and plays a role in regulating oxidative stress. The aim of this study was to explore the potential role of CAV1 on oxidative stress and autophagy during a high NEFA challenge in the immortalized bovine mammary epithelial cell line MAC-T. Mammary gland tissue biopsies and blood samples were collected from healthy (n = 15) and clinically ketotic (n = 15) Holstein cows at 3 to 10 (average = 6) days in milk. Compared with healthy cows, ketotic cows had lower dry matter intake (DMI), daily milk yield, serum glucose and greater serum NEFA and BHBA, accompanied by greater milk fat and lower milk protein. Malondialdehyde (MDA) was greater but activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH) were lower in cows with clinical ketosis. A lower protein abundance of CAV1, Beclin 1, autophagy relative gene 5 (ATG5), and microtubule-associated protein 1 light chain 3 (LC3) as well as greater protein abundance of sequestosome-1 (SQSTM1, also called p62) were detected in mammary tissue of cows with clinical ketosis. In vitro, the MAC-T cells were treated with 0, 0.6 and 1.2 mM NEFA for 12 h or treated with 1.2 mM NEFA for various time points (0, 0.5, 1, 2, 4, 8, 12 and 24 h). Compared with 0 mM NEFA, protein abundance of CAV1, Beclin 1, ATG5 and LC3 was greater in the MAC-T challenged with 0.6 mM NEFA, but lower in the 1.2 mM NEFA group. Protein abundance of p62 was lower with 0.6 mM NEFA, but higher with 1.2 mM NEFA. In response to increasing doses of NEFA, mRNA abundance of CAV1, total antioxidant capacity (T-AOC) and SOD activity decreased while the level of reactive oxygen species (ROS) and content of MDA increased. The protein abundance of CAV1, Beclin 1, ATG5 and LC3 peaked at 0.5 h and 1 h, resulting in both linear and quadratic effects. The protein abundance of p62 decreased, reaching a nadir at 4 h in both a linear and quadratic manner. The silencing of CAV1 in MAC-T cells aggravated the 1.2 mM NEFA-induced decrease in Beclin 1 expression, impaired autophagy, and increase in oxidative stress, whereas the overexpression of CAV1 alleviated these effects. Pretreatment of MAC-T cells with Beclin 1 siRNA (si-Beclin 1) and overexpressing CAV1 followed by challenged with 1.2 mM NEFA reversed the CAV1 induced autophagy, thereby enhancing oxidative stress. Overall, these data suggest that CAV1 protects bovine mammary epithelial cells from NEFA-induced oxidative stress through enhancing the expression of Beclin 1 and activating autophagy., (© 2025, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Neuroinflammation and neurodegeneration are key processes that mediate the development and progression of neurological diseases. However, the mechanisms modulating these processes in different diseases remain incompletely understood. Advances in single cell based multi-omic analyses have helped to identify distinct molecular signatures such as Lgals3 that is associated with neuroinflammation and neurodegeneration in the central nervous system (CNS). Lgals3 encodes galectin-3 (Gal3), a β-galactoside and glycan binding glycoprotein that is frequently upregulated by reactive microglia/macrophages in the CNS during various neurological diseases. While Gal3 has previously been associated with non-CNS inflammatory and fibrotic diseases, recent studies highlight Gal3 as a prominent regulator of inflammation and neuroaxonal damage in the CNS during diseases such as multiple sclerosis, Alzheimer's disease, and Parkinson's disease. In this review, we summarize the pleiotropic functions of Gal3 and discuss evidence that demonstrates its detrimental role in neuroinflammation and neurodegeneration during different neurological diseases. We also consider the challenges of translating preclinical observations into targeting Gal3 in the human CNS., (Copyright © 2024 Copyright: © 2024 Neural Regeneration Research.)

In this Letter, an omni-directional reflector (ODR) with a thin hybrid dielectric layer (hybrid-ODR) is proposed to enhance the light extraction efficiency (LEE) for inclined-sidewall-shaped AlGaN-based deep ultraviolet light-emitting diode (DUV LED) by inserting a thin diamond with high refraction index into a conventional Al/Al 2 O 3 -based ODR. The three-dimensional finite-difference time-domain (3D FDTD) simulation results show that the LEE of TM-polarized light for the DUV LED with hybrid-ODR is enhanced by 18.5% compared with Al/Al 2 O 3 -based ODR. It is because the diamond can transform the evanescent wave in Al 2 O 3 into the propagating light wave in diamond, thereby preventing effective excitation of the surface plasmon polariton (SPP) on the surface of the metal Al. Moreover, the Brewster's angle effect causes the TM-polarized light in diamond to propagate effectively into AlGaN. Furthermore, decreasing the total thickness of the dielectric layer also improves the scattering effect of the inclined sidewall. However, the utilization of hybrid-ODR results in a slight reduction in the LEE for transverse electric (TE) polarized light because the light is confined to the diamond layer and eventually absorbed by the metal Al.

Microglia are tissue-resident macrophages of the central nervous system (CNS), performing numerous functions that support neuronal health and CNS homeostasis. They are a major population of immune cells associated with CNS disease activity, adopting reactive phenotypes that potentially contribute to neuronal injury during chronic neurodegenerative diseases such as multiple sclerosis (MS). The distinct mechanisms by which microglia regulate neuronal function and survival during health and disease remain limited due to challenges in resolving the complex in vivo interactions between microglia, neurons, and other CNS environmental factors. Thus, the in vitro approach of co-culturing microglia and neurons remains a valuable tool for studying microglia-neuronal interactions. Here, we present a protocol to generate and co-culture primary microglia and neurons from mice. Specifically, microglia were isolated after 9-10 days in vitro from a mixed glia culture established from brain homogenates derived from neonatal mice between post-natal days 0-2. Neuronal cells were isolated from brain cortices of mouse embryos between embryonic days 16-18. After 4-5 days in vitro, neuronal cells were seeded in 96-well plates, followed by the addition of microglia to form the co-culture. Careful timing is critical for this protocol as both cell types need to reach experimental maturity to establish the co-culture. Overall, this co-culture can be useful for studying microglia-neuron interactions and can provide multiple readouts, including immunofluorescence microscopy, live imaging, as well as RNA and protein assays.