PO-069 Treadmill exercise reduces Aβ deposition in the hippocampus of APP/PS1 mice by activating AMPK

Objective To investigate the molecular mechanism of AMPK-mediated motion reduction of Aβ deposition in the hippocampus of APP/PS1 mice. Methods The 3 months of C57BL/6 48 APP/PS1 mice and 48 wildtype mice were randomly divided into APP/PS1 quiet control group (ADC, n=24) and exercise group (ADE, n=24), wildtype quiet control group (the WTC, n=24) and exercise group (WTE, n=24).ADE and WTE groups performed 12 weeks of treadmill exercise, while ADC and WTC groups were placed in a quiet running platform environment. The contents of ATP, AMP in hippocampus were tested by ELISA, AMPK and BACE1 mRNA in hippocampus were tested by RT-qPCR, Protein expression of AMPK, Sirt1, PPARγ, PGC1α, BACE1, Aβ in hippocampus were tested by Western Blot, the hippocampus SPs were tested by immunohistochemical experiments. Results 12 weeks treadmill exercise can improve the AMP、ATP content, and the AMP/ATP ratio (p<0.05) in APP/PS1 mice hippocampus, up-regulation the mRNA and protein phosphorylation of AMPK(p<0.05),the protein expression of Sirt1、PPARγ and PGC1α(p<0.05)in APP/PS1 mice hippocampus, down-regulation the BACE1mRNA and protein expression levels (p<0.05), Aβ protein and SPs level (p<0.01) in APP/PS1 mice hippocampus. Conclusions The molecular mechanism of decrement Aβ deposition in APP/PS1 mice hippocampus mediated by 12 weeks of treadmill exercise may be related to activation of AMPK and the improvement of hippocampus energy metabolism by exercise, and then regulatiing the AMPK-BACE1 pathway

A Short-Armed Troodontid Dinosaur from the Upper Cretaceous of Inner Mongolia and Its Implications for Troodontid Evolution

BACKGROUND: The Troodontidae represents one of the most bird-like theropod groups and plays an important role in our understanding of avian origins. Although troodontids have been known for over 150 years, few known derived troodontid specimens preserve significant portions of both the forelimb and the hindlimb. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report a new troodontid taxon, Linhevenator tani gen. et sp. nov., based on a partial, semi-articulated skeleton recovered from the Upper Cretaceous Wulansuhai Formation of Wulatehouqi, Inner Mongolia, China. L. tani has an unusual combination of primitive and derived character states, though our phylogenetic analysis places it in a derived clade within the Troodontidae. As a derived taxon, L. tani has a dromaeosaurid-like pedal digit II, and this species also possesses a humerus that is proportionally much shorter and more robust than those of most other troodontids. CONCLUSION/SIGNIFICANCE: The combination of features present in Linhevenator indicates a complex pattern of character evolution within the Troodontidae. In particular, the discovery of Linhevenator suggests that derived troodontids have independently evolved a highly specialized pedal digit II and have significantly shortened the forelimb over the course of their evolution

Optical limiting using Laguerre-Gaussian beams

We demonstrate optical limiting using the self-lensing effect of a higher-order Laguerre-Gaussian beam in a thin dye-doped polymer sample, which we find is consistent with our model using Gaussian decomposition. The peak phase shift in the sample required for limiting is smaller than for a fundamental Gaussian beam with the added flexibility that the nonlinear medium can be placed either in front of or behind the beam focus.Comment: 3 pages, 4 figure

Determination of erlotinib in rabbit plasma by liquid chromatography mass spectrometry

A sensitive and selective liquid chromatography mass spectrometry (LC–MS) method for determination of erlotinib in rabbit plasma was developed. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 × 150 mm, 5 μm) column with acetonitrile-0.1 % formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) mode was used to quantification using target fragment ions m/z 394→336 for erlotinib and m/z 326→291 for the IS. Calibration plots were linear over the range of 5-2000 ng/mL for erlotinib in plasma. Lower limit of quantification (LLOQ) for erlotinib was 5 ng/mL. Mean recovery of erlotinib from plasma was in the range 84.5-95.7 %. CV of intra-day and interday precision were both less than 12 %. This method is simple and sensitive enough to be used in pharmacokinetic research for determination of erlotinib in rabbit plasma.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Determination of erlotinib in rabbit plasma by liquid chromatography mass spectrometry

A sensitive and selective liquid chromatography mass spectrometry (LC–MS) method for determination of erlotinib in rabbit plasma was developed. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1 × 150 mm, 5 μm) column with acetonitrile-0.1 % formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) mode was used to quantification using target fragment ions m/z 394→336 for erlotinib and m/z 326→291 for the IS. Calibration plots were linear over the range of 5-2000 ng/mL for erlotinib in plasma. Lower limit of quantification (LLOQ) for erlotinib was 5 ng/mL. Mean recovery of erlotinib from plasma was in the range 84.5-95.7 %. CV of intra-day and interday precision were both less than 12 %. This method is simple and sensitive enough to be used in pharmacokinetic research for determination of erlotinib in rabbit plasma.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Visualising Co nanoparticle aggregation and encapsulation in Co/TiO2 catalysts and its mitigation through surfactant residues

Due to the reducible nature of TiO2, the encapsulation of cobalt nanoparticles (CoNPs) by reduced TiO2-x is often reported to decrease their catalytic performance in reactions such as Fisher-Tropsch synthesis (FTS). Here, we show using HAADF-STEM imaging and electron energy loss spectroscopy (EELS) that a residual C12E4 surfactant used to prepare the CoNPs, remains on the surface of a TiO2 rutile support, preventing the formation of Ti3+/Ti2+ oxides and therefore TiO2-x migration. Furthermore, the presence of these surfactant residues prevents the coalescence and aggregation of CoNPs during catalyst preparation, maintaining the dispersion of CoNPs. As such, using C12E4 in the preparation of Co/TiO2 can be considered beneficial for producing a catalyst with a greater number of active Co species

One Possible Mechanism of Pulsed Dye Laser Treatment on Infantile Hemangioma: Induction of Endothelial Apoptosis and Serum vascular endothelial growth factor (VEGF) Level Changes

Introduction: Pulsed dye laser (PDL) is an important treatment for superficial infantile hemangioma, but few studies report on its cellular mechanism. The aim of this study was to evaluate alterations of serum vascular endothelial growth factor (VEGF) level in infantile hemangioma (IH) patients after laser treatment and effects of PDL irradiation on human umbilical vein endothelial cells (HUVECs) in vitro, as well as to explore the biomolecular mechanisms and ultrastructure changes of the PDL effect.Methods: 74 children with infant hemangioma including 45 patients in proliferating phase, 18 patients in involuting phase, 11 patients in involuted phase and 10 healthy children were engaged in this study. The plasma VEGF levels of children were measured with the enzyme-linked immunosorbent assay (ELISA). 24 hours after, HUVECs cultured in vitro were irradiated with PDL, cell apoptosis, mRNA levels of VEGF, and changes of ultrastructure were evaluated using flow cytometry, real-time reverse transcriptase polymerase chain reaction (RT-PCR), and transmission electron microscopy, respectively.Results: The serum VEGF concentrations in children with proliferating hemangiomas were significantly higher than in patients with involuting / involved hemangiomas and healthy patients. After receiving 3 laser treatments, the plasma VEGF levels of IH patients in proliferating hemangiomas decreased significantly. PDL irradiation could down-regulate VEGF mRNA expression of HUVECs, and increase cell apoptosis rate. Conclusion: The present study demonstrates that PDL irradiation imparts apoptosis induction effects on HUVECs in vitro. Furthermore, our results suggest that vascular endothelial growth factor may be of particular importance in pathophysiology and PDL treatment of hemangiomas, also serum VEGF levels may be used as an aid in the follow up of IH. This provides valuable evidence of the PDL effect on infantile hemangioma

Everything of Thoughts: Defying the Law of Penrose Triangle for Thought Generation

Recent advancements in Large Language Models (LLMs) have revolutionized decision-making by breaking down complex problems into more manageable language sequences referred to as ``thoughts''. An effective thought design should consider three key perspectives: performance, efficiency, and flexibility. However, existing thought can at most exhibit two of these attributes. To address these limitations, we introduce a novel thought prompting approach called ``Everything of Thoughts'' (XoT) to defy the law of ``Penrose triangle of existing thought paradigms. XoT leverages pretrained reinforcement learning and Monte Carlo Tree Search (MCTS) to incorporate external domain knowledge into thoughts, thereby enhancing LLMs' capabilities and enabling them to generalize to unseen problems efficiently. Through the utilization of the MCTS-LLM collaborative thought revision framework, this approach autonomously produces high-quality comprehensive cognitive mappings with minimal LLM interactions. Additionally, XoT empowers LLMs to engage in unconstrained thinking, allowing for flexible cognitive mappings for problems with multiple solutions. We evaluate XoT on several challenging multi-solution problem-solving tasks, including Game of 24, 8-Puzzle, and Pocket Cube. Our results demonstrate that XoT significantly outperforms existing approaches. Notably, XoT can yield multiple solutions with just one LLM call, showcasing its remarkable proficiency in addressing complex problems across diverse domains.Comment: 17 pages, 5 figure