Gradient boosting DD-MLP Net: An ensemble learning model using near-infrared spectroscopy to classify after-stroke dyskinesia degree during exercise.

This study aims to develop an automatic assessment of after-stroke dyskinesias degree by combining machine learning and near-infrared spectroscopy (NIRS). Thirty-five subjects were divided into five stages (healthy, patient: Brunnstrom stages 3, 4, 5, 6). NIRS was used to record the muscular hemodynamic responses from bilateral femoris (biceps brachii) muscles during passive and active upper (lower) limbs circular exercise. We used the D-S evidence theory to conduct feature information fusion and established a Gradient Boosting DD-MLP Net model, combining the dendrite network and multilayer perceptron, to realize automatic dyskinesias degree evaluation. Our model classified the upper limb dyskinesias with high accuracy: 98.91% under the passive mode and 98.69% under the active mode, and classified the lower limb dyskinesias with high accuracy: 99.45% and 99.63% under the passive and active modes, respectively. Our model combined with NIRS has great potential in monitoring the after-stroke dyskinesias degree and guiding rehabilitation training.

Age-related difference in muscle metabolism patterns during upper limb's encircling exercise: a near-infrared spectroscopy study.

Aging is usually accompanied by decrease in limb motor function and change in muscle metabolism patterns. However, few studies have investigated the aging effect on muscle hemodynamics of the upper extremity. This study aims to explore the aging effect on muscle metabolism patterns during upper limb's exercise. Twelve middle-aged and elderly subjects and 12 young subjects were recruited, and muscle oxygenation signals from these subjects' biceps brachii muscles were collected during active and passive upper limb's encircling exercise with near-infrared spectroscopy (NIRS). The old group showed stronger muscle hemodynamic metabolism than the young group. The multiscale fuzzy approximate entropy and multiscale transfer entropy analyses indicated higher complexity and stronger interlimb coupling of the muscle oxygenation signals for the old group. Based on the selected muscle metabolism features, the constructed support vector machine model showed a high accuracy rate for classifying the two groups of subjects: 91.6% for the passive mode and 87.5% for the active mode. Our results proved the specific muscle metabolism patterns in the upper limb's exercise for old subjects, promoting the understanding of the aging effect on muscle hemodynamics.

Translocator protein (18 kDa) regulates the microglial phenotype in Parkinson's disease through P47.

Numerous studies have suggested that the phenotypic transformation of microglia plays a role in the pathogenesis of Parkinson's disease (PD). Translocator protein (TSPO) is an 18 kDa translocator membrane protein that acts as a marker of neuroinflammation and suppresses neuroinflammation; however, its underlying mechanism remains unclear. Although TSPO ligands were found to be protective in several neurodegenerative paradigms, few studies have evaluated their effects on microglial polarization, and underlying mechanisms need to be explored. In the present study, we examined the effects of TSPO and PK11195, a TSPO ligand, on lipopolysaccharide (LPS)+interferon (IFN)-γ-induced inflammatory factors and oxidative stress in microglia using enzyme-linked immunosorbent assay. The effect of TSPO and PK11195 on LPS+IFN-γ-induced microglial cell apoptosis was examined using immunofluorescence (IF), flow cytometry, and western blotting. The interaction between TSPO and P47 was investigated using IF and co-immunoprecipitation analysis. In vivo experiments confirmed the influence of TSPO and its ligand on motility, a-Syn, and dopaminergic neuronal damage. Our findings indicate that TSPO may regulate the microglial phenotype in PD via P47, suggesting a potential role in anti-PD therapy.

Improvement mechanism of energy conversion efficiency in ultrasonic motor with flexible rotor.

Flexible rotors are widely used in traveling wave rotary ultrasonic motors (TRUMs) because of their higher energy conversion efficiency; however, there have been few reports on how flexible rotors improve the energy conversion efficiency of ultrasonic motors. In this study, we investigate the improvement mechanism of energy conversion efficiency in TRUMs with flexible rotors. A 3D finite element (FE) model with full coupling among a piezoelectric coupled stator, rotor, friction layer, and the rigid-elastic contact interface of the stator and friction layer is established. To analyze the mechanism by which the efficiency of the TRUM is improved, the contact interface and rotor vibration information are extracted. Taking TRUM-60 as an example, the transient solution method and modal analysis method are used to solve the model. It is found that when the stator mode is B09, the flexible rotor mode is B19. The energy conversion efficiency of the TRUM is obtained from the ratio of output power to the electrical input power of the model solution. The results are validated using 3D vibration measurements and energy conversion efficiency experiments. The simulation result shows that the motor with flexible rotor improves the energy conversion efficiency compared with the motor with rigid rotor, which can be attributed to two reasons: first, the axial amplitude ratio of the flexible rotor to the stator is reduced; second, the flexible rotor reduces the radial friction. This study reveals the influence of flexible rotor on the output efficiency and can thus provide guidance for rotor design.

Naloxone Protects against Lipopolysaccharide-Induced Neuroinflammation and Microglial Activation via Inhibiting ATP-Sensitive Potassium Channel.

AIM: The aim of this study was to evaluate the anti-inflammatory effects and underlying mechanism of naloxone on lipopolysaccharide- (LPS-) induced neuronal inflammation and microglial activation. METHODS: LPS-treated microglial BV-2 cells and mice were used to investigate the anti-inflammatory effects of naloxone. RESULTS: The results showed that naloxone dose-dependently promoted cell proliferation in LPS-induced BV-2 cells, downregulated the expression of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) and proinflammatory enzymes iNOS and COX-2 as well as the expression of free radical molecule NO, and reduced the expression of Iba-1-positive microglia in LPS-stimulated BV-2 cells and mouse brain. Moreover, naloxone improved LPS-induced behavior degeneration in mice. Mechanically, naloxone inhibited LPS-induced activation in the ATP-sensitive potassium (KATP) channel. However, the presence of glibenclamide (Glib), an antagonist of KATP channel, ameliorated the suppressive effects of naloxone on inflammation and microglial activation. CONCLUSION: Naloxone prevented LPS-induced neuroinflammation and microglial activation partially through the KATP channel. These findings might highlight the potential of naloxone in neuroinflammation therapy.

MiR-194-5p enhances the sensitivity of nonsmall-cell lung cancer to doxorubicin through targeted inhibition of hypoxia-inducible factor-1.

BACKGROUND: Despite chemotherapy being a common treatment, an increase in chemoresistance over time is unavoidable. We therefore investigated the role of miR-194-5p in regulating chordoma cell behavior and examined the downstream effectors of miR-194-5p. METHODS: In this study, NSCLC cell lines A549 and H460 were cultured under hypoxic conditions for 1 week to induce drug resistance to doxorubicin (DOX). The connection between miR-194-5p and HIF-1 was revealed by reverse transcription and real-time polymerase chain reaction (RT-qPCR), western blot, and dual-luciferase assays. We used TUNEL staining and the CCK-8 test to assess the sensitivity of NSCLC cells to DOX. RESULTS: We found that hypoxia-induced NSCLC cells enhanced resistance to DOX. MiR-194-5p was substantially reduced, and HIF-1 was increased in hypoxia-induced drug-resistant NSCLC cells. Moreover, miR-194-5p successfully induced NSCLC cell apoptosis by directly inhibiting HIF-1, thereby enhancing DOX sensitivity. CONCLUSIONS: MiR-194-5p enhanced the sensitivity of NSCLC cells to DOX by directly inhibiting HIF-1. This work provides insights into underlying treatments for drug-resistant NSCLC.

Detection of Plasma Catecholamines in Human Pheochromocytoma and Primary Hypertension Based on Liquid Chromatography Tandem Mass Spectrometry.

BACKGROUND: The measurement of plasma catecholamines (CAs) including dopamine (DA), epinephrine (E), and norepinephrine (NE) and their derivatives including metanephrine (MN), normetanephrine (NMN), vanillylmandelic acid (VMA), and homovanillic acid (HVA) has been used in the diagnosis of pheochromocytoma and paraganglioma (PPGL) and primary hypertension (PH) but are typically detected individually when clinical testing. In this study, pre-column derivatization with dansyl chloride (DNS-Cl) combined with an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to simultaneously quantify HVA, VMA, MN, NMN, DA, E, and NE in the plasma from patients with PPGL and PH. METHODS: Plasma samples were extracted by acetonitrile and derivatized with DNS-Cl, followed by reverse phase separation and triple quadruple detection. Quantification of the CAs and their derivatives in 10 PPGL, 10 PH, and 100 healthy subjects was performed by UPLC-MS/MS analysis. RESULTS: All the values of detected CAs/derivatives were in the linearity ranges of the fitted curves. The expression levels of the seven CAs in the PPGL and PH patients were significantly higher than the healthy controls, suggesting increased CA production in the former. There were significant differences in plasma NE, NMN, and VMA levels between the PPGL and PH patients, but there was no significant difference in plasma E, MN, DA, and HVA. A discriminant analysis showed that 90% of the final cases were classified correctly based on the detected CAs/derivatives. CONCLUSIONS: Our results show that the combined detection of the seven CAs/derivatives could be used for the clinical diagnosis of PPGL and PH.

Proanthocyanidins exert a neuroprotective effect via ROS/JNK signaling in MPTP­induced Parkinson's disease models in vitro and in vivo.

The pathological alterations of Parkinson's disease (PD) predominantly manifest as a loss of dopaminergic neurons in the substantia nigra, which may be caused by oxidative stress damage. Proanthocyanidins (PCs) are a class of compounds found in various plants, which have significant antioxidant and free radical­scavenging activity. The present study investigated the protective effects and underlying mechanisms of PCs in a 1­methyl­4­phenyl­1,2,3,6­tetrahydropyridine (MPTP)­induced PD model in vitro and in vivo. MTT assays were used to detect cell viability, and flow cytometry and TUNEL assays were used to detect cell apoptosis. Mitochondrial membrane potential (MMP) alterations were investigated using a JC­1 MMP Assay kit. The pole test was used to measure motor behavior in a mouse model of PD. Levels of reactive oxygen species (ROS) were measured using the fluorescent probe, 2',7'­dichlorodihydrofluorescein diacetate. Immunohistochemistry and western blotting were performed to detect the expression levels of proteins associated with PD. In vitro, it was demonstrated that in MPTP­treated PC12 cells, PCs increased cell viability and reduced cell apoptosis in a dose­dependent manner. In vivo, it was revealed that PC treatment inhibited striatal dopamine depletion, which resulted in significant improvements in PD­like movement impairment. Reactive oxygen species (ROS) production and MPTP­induced apoptosis were also inhibited. Furthermore, the results demonstrated that the neuroprotective activity of PCs may be mediated via the inhibition of ROS generation, as well as modulation of c­Jun N­terminal kinase activation. Taken together, these data revealed that PCs may exert neuroprotective effects in in vivo and in vitro PD models, and may have potential in the prevention or treatment of PD.

Hepcidin links gluco-toxicity to pancreatic beta cell dysfunction by inhibiting Pdx-1 expression.

OBJECTIVE: Gluco-toxicity is a term used to convey the detrimental effect of hyperglycemia on ß-cell function through impaired insulin synthesis. Although it is known that the expression and activity of several key insulin transcription regulators is inhibited, other molecular mechanisms that mediate gluco-toxicity are poorly defined. Our objective was to explore the role of hepcidin in ß-cell gluco-toxicity. DESIGN: We first confirmed that high glucose levels inhibited hepcidin expression in the mouse insulinoma cell line, MIN6. The downregulation of hepcidin decreased Pdx-1 expression, which reduced insulin synthesis. METHODS: MIN6 cells were exposed to high glucose concentrations (33.3 mmol/L). Glucose-stimulated insulin secretion (GSIS) and serum hepcidin levels were measured by ELISA. The mRNA levels of insulin1, insulin2, Pdx-1 and hepcidin were measured by real-time polymerase chain reaction. Western blot analysis was used to detect the changes in PDX-1 expression. Transient overexpression with hepcidin was used to reverse the downregulation of Pdx-1 and insulin synthesis induced by gluco-toxicity. RESULTS: Exposure of MIN6 cells to high glucose significantly decreased GSIS and inhibited insulin synthesis as well as Pdx-1 transcriptional activity and expression at both the mRNA and protein levels. High glucose also decreased hepcidin expression and secretion. Hepcidin overexpression in MIN6 cells partially reversed the gluco-toxicity-induced downregulation of Pdx-1 and insulin expression and improved GSIS. The restoration of insulin synthesis by transfection of a hepcidin overexpression plasmid confirmed the role of hepcidin in mediating the gluco-toxic inhibition of insulin synthesis. CONCLUSIONS: Our observations suggest that hepcidin is associated with gluco-toxicity-reduced pancreatic ß-cell insulin synthesis in type 2 diabetes by inhibiting Pdx-1 expression.