Harmine Ameliorates Cognitive Impairment by Inhibiting NLRP3 Inflammasome Activation and Enhancing the BDNF/TrkB Signaling Pathway in STZ-Induced Diabetic Rats

Diabetes mellitus (DM) is considered a risk factor for cognitive dysfunction. Harmine not only effectively improves the symptoms of DM but also provides neuroprotective effects in central nervous system diseases. However, whether harmine has an effect on diabetes-induced cognitive dysfunction and the underlying mechanisms remain unknown. In this study, the learning and memory abilities of rats were evaluated by the Morris water maze test. Changes in the nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and brain-derived neurotrophic factor (BDNF)/TrkB signaling pathway were determined in both streptozotocin (STZ)-induced diabetic rats and high glucose (HG)-treated SH-SY5Y cells by western blotting and histochemistry. Herein, we found that harmine administration significantly ameliorated learning and memory impairment in diabetic rats. Further study showed that harmine inhibited NLRP3 inflammasome activation, as demonstrated by reduced NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18 levels, in the cortex of harmine-treated rats with DM. Harmine was observed to have similar beneficial effects in HG-treated neuronal cells. Moreover, we found that harmine treatment enhanced BDNF and phosphorylated TrkB levels in both the cortex of STZ-induced diabetic rats and HG-treated cells. These data indicate that harmine mitigates cognitive impairment by inhibiting NLRP3 inflammasome activation and enhancing the BDNF/TrkB signaling pathway. Thus, our findings suggest that harmine is a potential therapeutic drug for diabetes-induced cognitive dysfunction

Comparison of Diagnostic Performance of Three-Dimensional Positron Emission Mammography versus Whole Body Positron Emission Tomography in Breast Cancer

Objective. To compare the diagnostic performance of three-dimensional (3D) positron emission mammography (PEM) versus whole body positron emission tomography (WBPET) for breast cancer. Methods. A total of 410 women with normal breast or benign or highly suspicious malignant tumors were randomized at 1 : 1 ratio to undergo 3D-PEM followed by WBPET or WBPET followed by 3D-PEM. Lumpectomy or mastectomy was performed on eligible participants after the scanning. Results. The sensitivity and specificity of 3D-PEM were 92.8% and 54.5%, respectively. WBPET showed a sensitivity of 95.7% and specificity of 56.8%. After exclusion of the patients with lesions beyond the detecting range of the 3D-PEM instrument, 3D-PEM showed higher sensitivity than WBPET (97.0% versus 95.5%, P = 0.913), particularly for small lesions (<1 cm) (72.0% versus 60.0%, P = 0.685). Conclusions. The 3D-PEM appears more sensitive to small lesions than WBPET but may fail to detect lesions that are beyond the detecting range. This study was approved by the Ethics Committee (E2012052) at the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China). The instrument positron emission mammography (PEMi) was approved by China State Food and Drug Administration under the registration number 20153331166

Activating TiO₂ through the Phase Transition-Mediated Hydrogen Spillover to Outperform Pt for Electrocatalytic pH-Universal Hydrogen Evolution.

Endowing conventional materials with specific functions that are hardly available is invariably of significant importance but greatly challenging. TiO2 is proven to be highly active for the photocatalytic hydrogen evolution while intrinsically inert for electrocatalytic hydrogen evolution reaction (HER) due to its poor electrical conductivity and unfavorable hydrogen adsorption/desorption behavior. Herein, the first activation of inert TiO2 for electrocatalytic HER is demonstrated by synergistically modulating the positions of d-band center and triggering hydrogen spillover through the dual doping-induced partial phase transition. The N, F co-doping-induced partial phase transition from anatase to rutile phase in TiO2 (AR-TiO2|(N,F)) exhibits extraordinary HER performance with overpotentials of 74, 80, and 142 mV at a current density of 10 mA cm-2 in 1.0 M KOH, 0.5 M H2SO4, and 1.0 M phosphate-buffered saline electrolytes, respectively, which are substantially better than pure TiO2, and even superior to the benchmark Pt/C catalysts. These findings may open a new avenue for the development of low-cost alternative to noble metal catalysts for electrocatalytic hydrogen production

Seasonal, Spatial Distribution and Ecological Risk Assessment of Heavy Metals in Surface Sediments from a Watershed Area in Gonghu Bay in Taihu Lake, China

Surface sediments from five stations within Gonghu Bay in Taihu Lake, China, were sampled for seasonal and spatial metal contamination analysis variations and ecological risks assessment from April 2009 to January 2010. The Contamination Factor (CF) and geo-accumulation index (Igeo) indicated that the sediments in Gonghu Bay ranged from unpolluted to moderately polluted, except for Cd. The one-way ANOVA analysis results showed that the Pb, Zn, Cr, and Cu concentrations were higher at station 3 (lake inlet) and the Cr, Pb, and Zn concentrations were significantly higher in the spring. Additionally, using BCR¡¦s sequential extraction, the results showed that the fractionated metals Zn and Cd were observed as bioavailable fractions in the sediments, which could have potential moderate mobility in the water system. There was a significant increase in the bioavailable form during winter. The ratio of secondary and primary phrase (RSP) decreased according to the order Zn > Cu > Ni > Pb > Cd > Cr. Finally, these results indicated that the sediments of Gonghu Bay were polluted by Cd, Zn, and Cu, which provides a scientific basis for effectively protecting sediments in watershed areas from long-term heavy metal accumulation

Inhibition of MicroRNA-96 Ameliorates Cognitive Impairment and Inactivation Autophagy Following Chronic Cerebral Hypoperfusion in the Rat

Background/Aims: Chronic cerebral hypoperfusion (CCH) is a high-risk factor for vascular dementia and Alzheimer’s disease. Autophagy plays a critical role in the initiation and progression of CCH. However, the underlying mechanisms remain unclear. In this study, we identified the effect of a microRNA (miR) on autophagy under CCH. Methods: A CCH rat model was established by two-vessel occlusion (2VO). Learning and memory abilities were assessed by the Morris water maze. The protein levels of LC3, beclin-1, and mTOR were detected by western blotting and immunofluorescence assays, miR-96 expression was assessed by real-time PCR, luciferase assays were used to determine the effect of miR-96 on the 3′ untranslated region (UTR) of mTOR, and the number of autophagosomes was examined by electron microscopy. Results: The level of miR-96 was significantly increased in 2VO rats, and inhibition of miR-96 ameliorated the cognitive impairment induced by 2VO. Furthermore, the number of LC3- and beclin-1-positive autophagosomes was increased in 2VO rats, and was decreased after miR-96 antagomir injection. However, the protein level of mTOR was reduced in 2VO rats, and it was down-regulated by miR-96 overexpression and up-regulated by miR-96 inhibition in 2VO rats and primary culture cells. Moreover, the luciferase activity of the 3′-UTR of mTOR was suppressed by miR-96, which was relieved by mutation of the miR-96 binding sites. Conclusion: Our study demonstrated that miR-96 may play a key role in autophagy under CCH by regulating mTOR; therefore, miR-96 may represent a potential therapeutic target for CCH

Efficacy mechanisms research progress of the active components in the characteristic woody edible oils

Woody edible oils are a type of vegetable oil. Woody edible oils like olive oil have greater quantities of unsaturated fatty acids (UFAs), particularly essential FAs, as well as vitamin E, phytosterols, and other nutrients that are becoming more vital in human health. As a result, finding high-quality woody oil resource plants is critical to ensuring enough edible oil supply. As six novel woody crops, Paeonia suffruticosa, Plukenetia volubilis, Acer truncatum, Olea europaea, Camellia sinensis, and Camellia oleifera are characterized by high oil production, widespread cultivation, adaptability, and various active ingredients. The six woody crop oils contain UFAs (e.g., α-linolenic acid, oleic acid, and linoleic acid), vitamin E, polyphenols, phytosterols, and so forth. The presence of these active ingredients confers anti-inflammatory, antioxidant, cholesterol and lipid metabolism regulating, blood lipid lowering, immune boosting, memory improving, intestinal flora regulating, and other properties to the oils, which are beneficial to body health. This article examined in depth the seed resources, FA composition, active component kinds, active ingredient efficacy mechanism, and physiological impacts of these six novel woody crop oils. These developments lay a solid platform for further study and development of these woody oil crops.This work was supported by the Key Research and Development Program of Zhejiang Province (No. 2021C02002), Zhejiang Provincial Natural Sciences Foundation of China under Grant (No. LZ22C200006), Top young talents of the ten thousand talents program of Zhejiang Province (ZJWR0308016), Key R&D projects in Zhejiang Province (2023C04010), and Zhejiang Basic Public Welfare Research Project (LGN21C200006). Agusti Romero acknowledges financial support from the CERCA Program from the Generalitat of Catalonia. We would like to thank all contributors of the current study for their concepts, ideas, contribution, and provision.info:eu-repo/semantics/publishedVersio