Levistilide A Exerts a Neuroprotective Effect by Suppressing Glucose Metabolism Reprogramming and Preventing Microglia Polarization Shift: Implications for Parkinson's Disease.

The microglia, displaying diverse phenotypes, play a significant regulatory role in the development, progression, and prognosis of Parkinson's disease. Research has established that glycolytic reprogramming serves as a critical regulator of inflammation initiation in pro-inflammatory macrophages. Furthermore, the modulation of glycolytic reprogramming has the potential to reverse the polarized state of these macrophages. Previous studies have shown that Levistilide A (LA), a phthalide component derived from Angelica sinensis, possesses a range of pharmacological effects, including anti-inflammatory, antioxidant, and neuroprotective properties. In our study, we have examined the impact of LA on inflammatory cytokines and glucose metabolism in microglia induced by lipopolysaccharide (LPS). Furthermore, we explored the effects of LA on the AMPK/mTOR pathway and assessed its neuroprotective potential both in vitro and in vivo. The findings revealed that LA notably diminished the expression of M1 pro-inflammatory factors induced by LPS in microglia, while leaving M2 anti-inflammatory factor expression unaltered. Additionally, it reduced ROS production and suppressed IκB-α phosphorylation levels as well as NF-κB p65 nuclear translocation. Notably, LA exhibited the ability to reverse microglial glucose metabolism reprogramming and modulate the phosphorylation levels of AMPK/mTOR. In vivo experiments further corroborated these findings, demonstrating that LA mitigated the death of TH-positive dopaminergic neurons and reduced microglia activation in the ventral SNpc brain region of the midbrain and the striatum. In summary, LA exhibited neuroprotective benefits by modulating the polarization state of microglia and altering glucose metabolism, highlighting its therapeutic potential.

Sweet potato yield and quality characteristics affected by different late-season irrigation levels.

BACKGROUND: Seasonal late-season water deficits negatively affect the yield and quality of sweet potatoes in northern China. However, the amount of late-season irrigation to achieve high yield and consistent quality storage root remains undetermined. We assessed the yield and some qualitative traits of sweet potatoes such as size, shape, skin/flesh colour and nutritional content, as influenced by five irrigation levels (T0: unirrigated control; T1: 33% ETc; T2: 75% ETc; T3: 100% ETc; and T4: 125% ETc). RESULTS: Late-season irrigation significantly increased yield and marketable yield. Yields for T2 and T3 were significantly higher than other treatments, whereas T2 had the highest Grade A rating in a 2-year test. The vertical length of storage roots gradually increased with an increase in irrigation level, whereas the maximum width remained unchanged. The proportion of long elliptic and elliptic storage roots also increased, whereas the proportion of ovate, obovate and round storage roots gradually decreased. The skin and flesh colours became more vivid as the level of irrigation increased, with the skin colour becoming redder and the flesh colour becoming more orange-yellow. The levels of carotenoids, vitamin C and soluble sugar were significantly higher in irrigated crops, with the highest vitamin C and soluble sugar levels in T2 and the highest carotenoid levels in T3 treatment. CONCLUSION: Taken together, these results demonstrate the potential of moderate irrigation in the late-season to improve both yield production and quality potential. The results are of great importance for improving the market value of sweet potatoes and increasing grower profits. © 2024 Society of Chemical Industry.

Fe,Ce Co-Doped Ni3S2/NiS Polymorphism Nanosheets with Improved Electrocatalytic Activity and Stability for Water Oxidation.

Balancing the relationship between electrocatalytic activity and stability of sulfide catalysts during oxygen evolution reaction (OER) has been attracting extensive research interest. Here, a simple electrodeposition-vulcanization two-step route was designed to successfully construct nickel foam supported sheet-like Fe,Ce-codoped Ni3S2/NiS polymorphism catalyst (labeled as Fe,Ce-Ni3S2/NiS/NF). Electrochemical measurements showed that the as-obtained Fe,Ce-Ni3S2/NiS/NF electrode presented excellent OER electrocatalytic performances. In 1 M KOH solution, merely 173 and 234 mV of overpotentials were required to deliver the current densities of 10 and 100 mA cm-2, respectively. Further investigations revealed that the Fe,Ce co-doping regulated the electron density around Ni, which promoted the conversion of Ni towards the higher valence state and simultaneously, avoided the stability decrease of the catalyst caused by excessive oxidation corrosion. Moreover, the defects generated during vulcanization also contributed to promoting water oxidation. The present work provides a facile and feasible approach to balance the relationship between the stability and the activity of sulfide catalysts for OER.

The Notch inhibitor, FLI-06, increases the chemosensitivity of head and neck Squamous cell carcinoma cells to taxanes-based treatment.

Aberration of Notch signaling is one of the key events involved in the development and progression of head and neck squamous cell carcinoma (HNSCC). The Notch pathway controls the tissue-specific differentiation of normal squamous epithelial cells and is frequently altered in squamous carcinomas, thus affecting their proliferation, growth, survival, and chemosensitivity or resistance against anti-cancer agents. In this study, we show that the use of novel, small-molecule inhibitors of Notch signaling, such as FLI-06, can have a beneficial effect on increasing the chemosensitivity of HNSCC to taxane-based chemotherapy. Inhibition of Notch signaling by FLI-06 alone virtually blocks the proliferation and growth of HNSCC cells in both 2D and 3D cultures and the zebrafish model, which is accompanied by down-regulation of key Notch target genes and proteins. Mechanistically, FLI-06 treatment causes cell cycle arrest in the G1-phase and induction of apoptosis in HNSCC, which is accompanied by increased c-JunS63 phosphorylation. Combining FLI-06 with Docetaxel shows a synergistic effect and partially blocks the cell growth of aggressive HNSCC cells via enhanced apoptosis and modification of c-JunS243 phosphorylation via GSK-3ß inhibition. In conclusion, inhibition of Notch signaling in HNSCC cells that retain active Notch signaling significantly supports taxane-based anticancer activities via modulation of both the GSK-3ß and the c-Jun.

Regional brain activity and connectivity associated with childhood trauma in drug-naive patients with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive, compulsive behaviors, with childhood trauma recognized as a contributing factor to its pathophysiology. This study aimed to delineate brain functional aberrations in OCD patients and explore the association between these abnormalities and childhood trauma, to gain insights into the neural underpinnings of OCD. Forty-eight drug-naive OCD patients and forty-two healthy controls (HC) underwent resting-state functional magnetic resonance imaging and clinical assessments, including the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Childhood Trauma Questionnaire-Short Form (CTQ-SF). Compared to HCs, OCD patients exhibited significantly decreased amplitude of low-frequency fluctuations (ALFF) in the right cerebellum, decreased regional homogeneity (ReHo) in the right cerebellum and right superior occipital lobes (FWE-corrected p < 0.05), which negatively correlated with Y-BOCS scores (p < 0.05). Furthermore, cerebellar ALFF negatively correlated with the CTQ emotional abuse subscale (r = - 0.514, p < 0.01). Mediation analysis revealed that cerebellar ALFF mediated the relationship between CTQ-emotional abuse and Y-BOCS (good model fit: R2 = 0.231, MSE = 14.311, F = 5.721, p < 0.01; direct effect, c' = 0.153, indirect effect, a*b = 0.191). Findings indicated abnormal spontaneous and regional cerebellar activity in OCD, suggesting childhood trauma impacts OCD symptoms through cerebellar neural remodeling, highlighting its importance for clinical treatment selection.

Traditional uses, phytochemistry, pharmacology, quality control and clinical studies of Cimicifugae Rhizoma: a comprehensive review.

Cimicifugae Rhizoma, generally known as "Sheng Ma" in China, has great medicinal and dietary values. Cimicifugae Rhizoma is the dried rhizome of Cimicifuga foetida L., Cimicifuga dahurica (Turcz.) Maxim. and Cimicifuga heracleifolia Kom., which has been used to treat wind-heat headache, tooth pain, aphtha, sore throat, prolapse of anus and uterine prolapse in traditional Chinese medicine. This review systematically presents the traditional uses, phytochemistry, pharmacology, clinical studies, quality control and toxicity of Cimicifugae Rhizoma in order to propose scientific evidence for its rational utilization and product development. Herein, 348 compounds isolated or identified from the herb are summarized in this review, mainly including triterpenoid saponins, phenylpropanoids, chromones, alkaloids, terpenoids and flavonoids. The crude extracts and its constituents had various pharmacological properties such as anti-inflammatory, antitumor, antiviral, antioxidant, neuroprotective, anti-osteoporosis and relieving menopausal symptoms. The recent research progress of Cimicifugae Rhizoma in ethnopharmacology, phytochemistry and pharmacological effects demonstrates the effectiveness of its utilization and supplies valuable guidance for further research. This review will provide a basis for the future development and utilization of Cimicifugae Rhizoma.