Precious but convenient means of prevention and treatment: physiological molecular mechanisms of interaction between exercise and motor factors and Alzheimer’s disease

Disproportionate to the severity of Alzheimer’s disease (AD) and the huge number of patients, the exact treatment and prevention of AD is still being explored. With increasing ageing, the search for means to prevent and treat AD has become a high priority. In the search for AD, it has been suggested that exercise may be one of the more effective and less costly means of preventing and treating AD, and therefore a large part of current research is aimed at exploring the effectiveness of exercise in the prevention and treatment of AD. However, due to the complexity of the specific pathogenesis of AD, there are multiple hypotheses and potential mechanisms for exercise interventions in AD that need to be explored. This review therefore specifically summarises the hypotheses of the interaction between exercise and AD from a molecular perspective, based on the available evidence from animal models or human experiments, and explores them categorised according to the pathologies associated with AD: exercise can activate a number of signalling pathways inhibited by AD (e.g., Wnt and PI3K/Akt signalling pathways) and reactivate the effects of downstream factors regulated by these signalling pathways, thus acting to alleviate autophagic dysfunction, relieve neuroinflammation and mitigate Aβ deposition. In addition, this paper introduces a new approach to regulate the blood-brain barrier, i.e., to restore the stability of the blood-brain barrier, reduce abnormal phosphorylation of tau proteins and reduce neuronal apoptosis. In addition, this paper introduces a new concept.” Motor factors” or “Exerkines”, which act on AD through autocrine, paracrine or endocrine stimulation in response to movement. In this process, we believe there may be great potential for research in three areas: (1) the alleviation of AD through movement in the brain-gut axis (2) the prevention and treatment of AD by movement combined with polyphenols (3) the continued exploration of movement-mediated activation of the Wnt signalling pathway and AD

Adaptive Sliding Mode Control of Mobile Manipulators with Markovian Switching Joints

The hybrid joints of manipulators can be switched to either active (actuated) or passive (underactuated) mode as needed. Consider the property of hybrid joints, the system switches stochastically between active and passive systems, and the dynamics of the jump system cannot stay on each trajectory errors region of subsystems forever; therefore, it is difficult to determine whether the closed-loop system is stochastically stable. In this paper, we consider stochastic stability and sliding mode control for mobile manipulators using stochastic jumps switching joints. Adaptive parameter techniques are adopted to cope with the effect of Markovian switching and nonlinear dynamics uncertainty and follow the desired trajectory for wheeled mobile manipulators. The resulting closed-loop system is bounded in probability and the effect due to the external disturbance on the tracking errors can be attenuated to any preassigned level. It has been shown that the adaptive control problem for the Markovian jump nonlinear systems is solvable if a set of coupled linear matrix inequalities (LMIs) have solutions. Finally, a numerical example is given to show the potential of the proposed techniques

Learning Unorthogonalized Matrices for Rotation Estimation

Estimating 3D rotations is a common procedure for 3D computer vision. The accuracy depends heavily on the rotation representation. One form of representation -- rotation matrices -- is popular due to its continuity, especially for pose estimation tasks. The learning process usually incorporates orthogonalization to ensure orthonormal matrices. Our work reveals, through gradient analysis, that common orthogonalization procedures based on the Gram-Schmidt process and singular value decomposition will slow down training efficiency. To this end, we advocate removing orthogonalization from the learning process and learning unorthogonalized `Pseudo' Rotation Matrices (PRoM). An optimization analysis shows that PRoM converges faster and to a better solution. By replacing the orthogonalization incorporated representation with our proposed PRoM in various rotation-related tasks, we achieve state-of-the-art results on large-scale benchmarks for human pose estimation

Unravelling the Impact of Palladium on Ruthenium-Induced Corrosion of SiC Coating

This study investigates the corrosion behaviour of fission products (FPs) on SiC layers of tri-structural isotropic (TRISO) particles. Specifically, it explores the effects of Pd (strongly reactive FP) on Ru (weakly reactive FP)-induced corrosion. Ru silicides formed after Ru-SiC reactions at 1300/1500°C. In Pd-Ru/SiC systems, a Ru-Pd-Si liquid phase forms at high temperatures even with minimal Pd, accelerating corrosion along SiC grain boundaries. Comparing Pd’s role in Ru/SiC and Ag/SiC systems underscores the importance of liquid phases in FP migration. A novel approach is proposed for predicting the corrosion effects of multiple FPs on SiC through enthalpic interaction analysis.<br/

TGFB-INHB/activin signaling regulates age-dependent autophagy and cardiac health through inhibition of MTORC2 Autophagy

Age-related impairment of macroautophagy/autophagy and loss of cardiac tissue homeostasis contribute significantly to cardiovascular diseases later in life. MTOR (mechanistic target of rapamycin kinase) signaling is the most well-known regulator of autophagy, cellular homeostasis, and longevity. The MTOR signaling consists of two structurally and functionally distinct multiprotein complexes, MTORC1 and MTORC2. While MTORC1 is well characterized but the role of MTORC2 in aging and autophagy remains poorly understood. Here we identified TGFB-INHB/activin signaling as a novel upstream regulator of MTORC2 to control autophagy and cardiac health during aging. Using Drosophila heart as a model system, we show that cardiac-specific knockdown of TGFB-INHB/activin-like protein daw induces autophagy and alleviates age-related heart dysfunction, including cardiac arrhythmias and bradycardia. Interestingly, the downregulation of daw activates TORC2 signaling to regulate cardiac autophagy. Activation of TORC2 alone through overexpressing its subunit protein rictor promotes autophagic flux and preserves cardiac function with aging. In contrast, activation of TORC1 does not block autophagy induction in daw knockdown flies. Lastly, either daw knockdown or rictor overexpression in fly hearts prolongs lifespan, suggesting that manipulation of these pathways in the heart has systemic effects on longevity control. Thus, our studies discover the TGFB-INHB/activin-mediated inhibition of TORC2 as a novel mechanism for age-dependent decreases in autophagic activity and cardiac health

Lipopolysaccharide-Induced Dephosphorylation of AMPK-Activated Protein Kinase Potentiates Inflammatory Injury via Repression of ULK1-Dependent Autophagy

AMP-activated protein kinase (AMPK) is a crucial metabolic regulator with profound modulatory activities on inflammation. Although the anti-inflammatory benefits of AMPK activators were well documented in experimental studies, the pathological significance of endogenous AMPK in inflammatory disorders largely remains unknown. This study investigated the phosphorylation status of endogenous AMPK and the potential roles of AMPK in mice with lipopolysaccharide (LPS)-induced lethal inflammation. The results indicated that LPS dose-dependently decreased the phosphorylation level of AMPK and its target protein acetyl-CoA carboxylase (ACC). Reactivation of AMPK with the AMPK activator A-769662 suppressed LPS-induced elevation of interleukin 6, alleviated histological abnormalities in lung and improved the survival of LPS-challenged mice. Treatment with A-769662 restored LPS-induced suppression of autophagy, inhibition of autophagy by 3-MA reversed the beneficial effects of A-769662. Treatment with A-769662 suppressed LPS-induced activation of mammalian target of rapamycin (mTOR), co-administration of mTOR activator abolished the beneficial effects of A-769662, and the suppressive effects of A-769662 on uncoordinated-51-like kinase 1 (ULK1) phosphorylation. Inhibition of ULK1 removed the beneficial effects of A-769662. These data indicated that LPS-induced dephosphorylation of AMPK could result in weakened inhibition of mTOR and repression of ULK1-dependent autophagy, which might potentiate the development of LPS-induced inflammatory injury. These data suggest that pharmacological restoration of AMPK activation might be a beneficial approach for the intervention of inflammatory disorders

MRI radiomics-based decision support tool for a personalized classification of cervical disc degeneration: a two-center study

Objectives: To develop and validate an MRI radiomics-based decision support tool for the automated grading of cervical disc degeneration.Methods: The retrospective study included 2,610 cervical disc samples of 435 patients from two hospitals. The cervical magnetic resonance imaging (MRI) analysis of patients confirmed cervical disc degeneration grades using the Pfirrmann grading system. A training set (1,830 samples of 305 patients) and an independent test set (780 samples of 130 patients) were divided for the construction and validation of the machine learning model, respectively. We provided a fine-tuned MedSAM model for automated cervical disc segmentation. Then, we extracted 924 radiomic features from each segmented disc in T1 and T2 MRI modalities. All features were processed and selected using minimum redundancy maximum relevance (mRMR) and multiple machine learning algorithms. Meanwhile, the radiomics models of various machine learning algorithms and MRI images were constructed and compared. Finally, the combined radiomics model was constructed in the training set and validated in the test set. Radiomic feature mapping was provided for auxiliary diagnosis.Results: Of the 2,610 cervical disc samples, 794 (30.4%) were classified as low grade and 1,816 (69.6%) were classified as high grade. The fine-tuned MedSAM model achieved good segmentation performance, with the mean Dice coefficient of 0.93. Higher-order texture features contributed to the dominant force in the diagnostic task (80%). Among various machine learning models, random forest performed better than the other algorithms (p &lt; 0.01), and the T2 MRI radiomics model showed better results than T1 MRI in the diagnostic performance (p &lt; 0.05). The final combined radiomics model had an area under the receiver operating characteristic curve (AUC) of 0.95, an accuracy of 89.51%, a precision of 87.07%, a recall of 98.83%, and an F1 score of 0.93 in the test set, which were all better than those of other models (p &lt; 0.05).Conclusion: The radiomics-based decision support tool using T1 and T2 MRI modalities can be used for cervical disc degeneration grading, facilitating individualized management

Lattice-contraction triggered synchronous electrochromic actuator.

Materials with synchronous capabilities of color change and actuation have prospects for application in biomimetic dual-stealth camouflage and artificial intelligence. However, color/shape dual-responsive devices involve stimuli that are difficult to control such as gas, light or magnetism, and the devices show poor coordination. Here, a flexible composite film with electrochromic/actuating (238° bending angle) dual-responsive phenomena, excellent reversibility, high synchronization, and fast response speed (< 5 s) utilizes a single active component, W18O49 nanowires. From in situ synchrotron X-ray diffraction, first principles calculations/numerical simulations, and a series of control experiments, the actuating mechanism for macroscopic deformation is elucidated as pseudocapacitance-based reversible lattice contraction/recovery of W18O49 nanowires (i.e. nanostructure change at the atomic level) during lithium ion intercalation/de-intercalation. In addition, we demonstrate the W18O49 nanowires in a solid-state ionic polymer-metal composite actuator that operates stably in air with a significant pseudocapacitive actuation