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Background: Chronic migraine (CM) is a debilitating neurofunctional disorder primarily affecting females, characterized by central sensitization. Central sensitization refers to the enhanced response to sensory stimulation, which involves changes in neuronal excitability, synaptic plasticity, and neurotransmitter release. Environmental enrichment (EE) can increase the movement, exploration, socialization and other behaviors of mice. EE has shown promising effects in various neurological disorders, but its impact on CM and the underlying mechanism remains poorly understood. Therefore, the purpose of this study was to determine whether EE has the potential to serve as a cost-effective intervention strategy for CM. Methods: A mouse CM model was successfully established by repeated administration of nitroglycerin (NTG). We selected adult female mice around 8 weeks old, exposed them to EE for 2 months, and then induced the CM model. Nociceptive threshold tests were measured using Von Frey filaments and a hot plate. The expression of c-Fos, calcitonin gene-related peptide (CGRP) and inflammatory response were measured using WB and immunofluorescence to evaluate central sensitization. RNA sequencing was used to find differentially expressed genes and signaling pathways. Finally, the expression of the target differential gene was investigated. Results: Repeated administration of NTG can induce hyperalgesia in female mice and increase the expression of c-Fos and CGRP in the trigeminal nucleus caudalis (TNC). Early exposure of mice to EE reduced NTG-induced hyperalgesia in CM mice. WB and immunofluorescence revealed that EE inhibited the overexpression of c-Fos and CGRP in the TNC of CM mice and alleviated the inflammatory response of microglia activation. RNA sequencing analysis identified that several central sensitization-related signaling pathways were altered by EE. VGluT1, a key gene involved in behavior, internal stimulus response, and ion channel activity, was found to be downregulated in mice exposed to EE. Conclusion: EE can significantly ameliorate hyperalgesia in the NTG-induced CM model. The mechanisms may be to modulate central sensitization by reducing the expression of CGRP, attenuating the inflammatory response, and downregulating the expression of VGluT1, etc., suggesting that EE can serve as an effective preventive strategy for CM. [ABSTRACT FROM AUTHOR]

• A truncated endo -α(1 → 3)-fucoidanase was expressed and characterized in detail. • Catalytic residues of endo -α(1 → 3)-fucoidanase were identified and confirmed. • Degraded products of fucoidan by α(1 → 3)-fucoidanase were characterized by ESI-MS2. • Kjellmaniella crassifolia fucoidan is complex and composed of α(1 → 3) linked l -fucose. Endo -fucoidanases are important in structural analysis of fucoidans and preparation of fuco-oligosaccharides. However their enzymological properties and analysis of degradation products are scarcely investigated. Truncated endo - α (1 → 3)-fucoidanase Fda1 (tFda1B from Alteromonas sp. was overexpressed and characterized, showing highest activity at pH 7.0, 35 °C, and 1.0 M NaCl. Its K m and k cat were 3.88 ± 0.81 mg/mL and 0.82 ± 0.17 min−1. Fe3+ and Mn2+ enhanced activity by 100% and 19.5% respectively. Co2+ and Cu2+ completely inactivated tFda1B, whereas Ni2+, Mg2+, Zn2+, Pb2+, Ca2+, Ba2+ and Li+ decreased activity by 58.8%, 56.0%, 50.6%, 47.7%, 28.9%, 15.6% and 37.5%, respectively. Catalytic residues were identified through structure and sequence alignment, and confirmed by mutagenesis. Degradation products of Kjellmaniella crassifolia fucoidan by tFda1B were characterized by LC-ESI-MS/MS, confirming tFda1B belongs to endo -(1 → 3)-fucoidanases, and backbone of K. crassifolia fucoidan is 1 → 3 fucoside linkage. This endo - α (1 → 3)-fucoidanase would be useful for elucidating fucoidan structures, and be used as a food enzyme. [ABSTRACT FROM AUTHOR]

Background: Chronic migraine is a common and highly disabling disorder. Functional MRI has indicated that abnormal brain region activation is linked with chronic migraine. Drugs targeting the calcitonin gene-related peptide (CGRP) or its receptor have been reported to be efficient for treating chronic migraine. The CGRP signaling was also shared in two types of chronic migraine models (CMMs). However, it remains unclear whether the activation of specific brain regions could contribute to persistent behavioral sensitization, and CGRP receptor antagonists relieve migraine-like pain in CMMs by altering specific brain region activation. Therefore, it’s of great interest to investigate brain activation pattern and the effect of olcegepant (a CGRP receptor-specific antagonist) treatment on alleviating hyperalgesia by altering brain activation in two CMMs, and provide a reference for future research on neural circuits. Methods: Repeated administration of nitroglycerin (NTG) or levcromakalim (LEV) was conducted to stimulate human migraine-like pain and establish two types of CMMs in mice. Mechanical hypersensitivity was evaluated by using the von Frey filament test. Then, we evaluated the activation of different brain regions with c-Fos and NeuN staining. Olcegepant was administered to explore its effect on mechanical hyperalgesia and brain region activation. Results: In two CMMs, acute and basal mechanical hyperalgesia was observed, and olcegepant alleviated mechanical hyperalgesia. In the NTG-induced CMM, the medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and the caudal part of the spinal trigeminal nucleus (Sp5c) showed a significant increase of c-Fos expression in the NTG group (p < 0.05), while pre-treatment with olcegepant reduced c-Fos expression compared with NTG group (p < 0.05). No significant difference of c-Fos expression was found in the paraventricular thalamic nucleus (PVT) and ventrolateral periaqueductal gray (vlPAG) between the vehicle control and NTG group (p > 0.05). In the LEV-induced CMM, mPFC, PVT, and Sp5c showed a significant increase of c-Fos expression between vehicle control and LEV group, and olcegepant reduced c-Fos expression (p < 0.05). No significant difference in c-Fos expression was found in vlPAG and ACC (p > 0.05). Conclusions: Our study demonstrated the activation of mPFC and Sp5c in two CMMs. Olcegepant may alleviate hyperalgesia of the hind paw and periorbital area by attenuating brain activation in CMMs. [ABSTRACT FROM AUTHOR]

Migraine is a complex neurological disease of unknown etiology involving both genetic and environmental factors. It has previously been reported that persistent pain may be mediated by the immune and inflammatory systems. Toll-like receptors (TLRs) play a significant role in immune and inflammatory responses and are expressed by microglia and astrocytes. One of the fundamental mechanisms of the innate immune system in coordinating inflammatory signal transduction is through TLRs, which protect the host organism by initiating inflammatory signaling cascades in response to tissue damage or stress. TLRs reside at the neuroimmune interface, and accumulating evidence has suggested that the inflammatory consequences of TLR activation on glia (mainly microglia and astrocytes), sensory neurons, and other cell types can influence nociceptive processing and lead to pain. Several studies have shown that TLRs may play a key role in neuropathic pain and migraine etiology by activating the microglia. The pathogenesis of migraine may involve a TLR-mediated crosstalk between neurons and immune cells. Innate responses in the central nervous system (CNS) occur during neuroinflammatory phenomena, including migraine. Antigens found in the environment play a crucial role in the inflammatory response, causing a broad range of diseases, including migraines. These can be recognized by several innate immune cells, including macrophages, microglia, and dendritic cells, and can be activated through TLR signaling. Given the prevalence of migraine and the insufficient efficacy and safety of current treatment options, a deeper understanding of TLRs is expected to provide novel therapies for managing chronic migraine. This review aimed to justify the view that TLRs may be involved in migraine. [ABSTRACT FROM AUTHOR]

• The P-P value of defect signal decreases with the increase of detection speed. • There is a speed limit at which the defect cannot be detected. • The quantitative evaluation at different speeds shows the relative error is in 15%. In this paper, the effects of detection speed on eddy current testing (ECT) signals are studied, and the quantitative evaluation method of rail surface cracks at different speeds is proposed. According to the finite element simulation analysis, the excitation frequency and coil parameters are optimized. A differential ECT system is established for rail crack detection experiments in a lift-off range of 1–6 mm and a speed range of 20–300 km/h. The experiment results show that the frequency of defect signal can be estimated by the coil diameter and the detection speed. The decrease trend of the defect signal amplitude with the increase of lift-off remains the same under different speeds. The defect signal amplitude decreases approximately linearly as the speed increases, and the decline slope is related to the defect depth. The relationship between the defect signal amplitude, the defect depth, and the detection speed is further obtained, which is used to evaluate the defect depth at different speed. [ABSTRACT FROM AUTHOR]

• Copper cations of bronze corrosion products were concentrated into the middle lamella (ML) of cell walls, and intensively fixed on the surface of cell lumen. • Cellulose was well-preserved in archaeological wood contaminated by copper corrosion, but lignin was severely degraded. • Iron underwent an intense Fenton reaction and produced hydroxyl radicals, resulting in wood polymer degradation accelerating. The deterioration mechanism of wooden archaeological artifacts inside the bronze of excavated chariots is not understood because it is unknown how bronze corrosion products affect the degradation of archaeological wood. In this paper, several microtopography and chemical analysis methods were used to characterize changes in the hierarchical structures and analyze the deterioration mechanisms of archaeological wood inside the bronze parts of chariots. The results indicated that some important components of chariots in ancient China mainly were made of Ulmus spp. and Pteroceltis tatarinowii woods due to their higher strength and good wear resistance in ancient traditional timber tree species. Furthermore, cellulose was well-preserved in archaeological wood contaminated by copper corrosion, especially crystalline cellulose, but lignin and hemicelluloses were severely degraded. The crystallite thickness and crystallinity of cellulose were also higher than those of more recent wood, but the arrangement of cellulose was disoriented. Copper cations of bronze corrosion products were concentrated into the middle lamella (ML) of cell walls and fixed on the inner surface of cell lumen. The micro-distributions of copper and lignin were correlated. However, iron components embedded in bronze underwent an intense Fenton reaction and produced hydroxyl radicals that penetrated the wood and accelerated wood polymer degradation. With an understanding of this deterioration mechanism, it is possible to determine possible conservation and preservation methods, including the development of copper preservatives and the desalination of iron compounds. [ABSTRACT FROM AUTHOR]