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Objective This study was designed to investigate the therapeutic efficacy and underlying mechanisms of Gandou Decoction (GDD) in copper-laden hepatolenticular degeneration (HLD) model rats. Methods In this study, high-performance liquid chromatography (HPLC) fingerprint analysis and eight representative active components were simultaneously measured for quality control of GDD. The therapeutic effect of GDD in HLD was studied by constructing a rat model of copper-laden HLD. The copper levels in the liver, serum, urine, and feces were quantified by atomic absorption spectrophotometry (AAS). Subsequently, UV-Vis spectrophotometry was used to study the coordination ability of copper ion (Cu2+) with six representative active components in GDD to explore its potential copper expulsion mechanism. Serological indexes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AKP) were evaluated. Hepatic indicators including superoxide dismutase (SOD), glutathione (GSH), and ced by excessive copper. Additionally, the hepatoprotective effect of GDD was also evidenced by the results of the liver histological evaluation. Conclusions This study suggested that GDD could reduce the serum and hepatic copper levels through promoting urinary and fecal copper excretion in copper-laden rats. At the same time, GDD could alleviate hepatic injury by inhibition of oxidative stress.Aim Angiogenesis plays an important role in the initiation, development, and metastasis of malignant tumors. Antiangiogenic drugs combined with immune therapy are considered to have a synergistic effect on anti-tumor strategy. Weichang'an formula (WCAF) is a prescription of traditional Chinese medicine (TCM) based on pharmaceutical screening and clinical experience. The aim of this study is to examine the effect of WCAF and its combined action with Bevacizumab (BEV) in colorectal cancer, and to identify the possible mechanism of action. Methods A human colon cancer cell (HCT 116) subcutaneous xenograft model was established in BALB/c-nu/nu mice. Tumor-bearing mice were randomized into each of four groups control, WCAF treated, BEV treated, and WCAF plus BEV treated. Apoptosis was detected by TUNEL assay. Western blot was used to assess the protein levels of Leptin-R, STAT3, p-STAT3, BCL-2, and VEGFR-1. Immunohistochemistry was used to detect the micro-vessel density (MVD) and AKT1. Leptin and Vascular endotheclusion WCAF can inhibit tumor growth and promote apoptosis and inhibit tumor angiogenesis in subcutaneous xenografts of human colon cancer HCT-116 in nude mice. WCAF also makes up for the deficiency of BEV by inhibiting VEGFR-1. The VEGFR-1 expression between the combination group and BEV alone achieved statistically significant difference (p less then 0.01). Combined with BEV, WCAF showed a partial additive anti-tumor effect. The mechanism may be related to Leptin/STAT3 signal transduction, VEGF-A, VEGFR-1 and WCAF target proteins related to cancer immune such as leptin and AKT1.Several studies of Parkinson's disease (PD) have reported dysregulation of cerebral metals, particularly decreases in copper and increases in iron in substantia nigra (SN). However, few studies have investigated regions outside the SN, fewer have measured levels of multiple metals across different regions within the same brains, and there are no currently-available reports of metal levels in Parkinson's disease dementia (PDD). This study aimed to compare concentrations of nine essential metals across nine different brain regions in cases of PDD and controls. Investigated were primary motor cortex (MCX); cingulate gyrus (CG); primary visual cortex (PVC); hippocampus (HP); cerebellar cortex (CB); SN; locus coeruleus (LC); medulla oblongata (MED); and middle temporal gyrus (MTG), thus covering regions with severe, moderate, or low levels of neuronal loss in PDD. Levels of eight essential metals and selenium were determined using an analytical methodology involving the use of inductively-coupled plasma mass spectementias.Background The reticulospinal tract (RST) is essential for balance, posture, and strength, all functions which falter with age. We hypothesized that age-related strength reductions might relate to differential changes in corticospinal and reticulospinal connectivity. Methods We divided 83 participants (age 20-84) into age groups less then 50 (n = 29) and ≥50 (n = 54) years; five of which had probable sarcopenia. Transcranial Magnetic Stimulation (TMS) was applied to the left cortex, inducing motor evoked potentials (MEPs) in the biceps muscles bilaterally. Contralateral (right, cMEPs) and ipsilateral (left, iMEPs) MEPs are carried by mainly corticospinal and reticulospinal pathways respectively; the iMEP/cMEP amplitude ratio (ICAR) therefore measured the relative importance of the two descending tracts. Grip strength was measured with a dynamometer and normalized for age and sex. Results We found valid iMEPs in 74 individuals (n = 44 aged ≥50, n = 29 less then 50). [https://www.selleckchem.com/products/ferrostatin-1.html Ferrostatin-1] Younger adults had a significant negative correlation between normalized grip strength and ICAR (r = -0.37, p = 0.045); surprisingly, in older adults, the correlation was also significant, but positive (r = 0.43, p = 0.0037). Discussion Older individuals who maintain or strengthen their RST are stronger than their peers. We speculate that reduced RST connectivity could predict those at risk of age-related muscle weakness; interventions that reinforce the RST could be a candidate for treatment or prevention of sarcopenia.Manual ELISA assays are the most commonly used methods for quantification of biomarkers; however, they often show inter- and intra-laboratory variability that limits their wide use. Here, we compared the Innotest ELISA method with two fully automated platforms (Lumipulse and Elecsys) to determine whether these new methods can provide effective substitutes for ELISA assays. We included 149 patients with AD (n = 34), MCI (n = 94) and non-AD dementias (n = 21). Aβ42, T-tau, and P-tau were quantified using the ELISA method (Innotest, Fujirebio Europe), CLEIA method on a Lumipulse G600II (Fujirebio Diagnostics), and ECLIA method on a Cobas e 601 (Roche Diagnostics) instrument. We found a high correlation between the three methods, although there were systematic differences between biomarker values measured by each method. Both Lumipulse and Elecsys methods were highly concordant with clinical diagnoses, and the combination of Lumipulse Aβ42 and P-tau had the highest discriminating power (AUC 0.915, 95% CI 0.822-1.ed platforms were standardized for reference samples, their use is recommended for the measurement of CSF AD biomarkers compared with unstandardized manual methods, such as Innotest ELISA, that have demonstrated a high inter and intra-laboratory variability.Background Behavioral and psychological symptoms of dementia (BPSD) are a distressful condition. We aimed to investigate the BPSD distribution in subjects with cognitive impairment, and the potential correlations between BPSD and neurodegeneration in terms of cerebrospinal fluid (CSF) tau and brain atrophy. Methods One-hundred patients with mild cognitive impairment (MCI) or dementia (Alzheimer's disease, AD; Lewy-body disease, LBD; frontotemporal dementia, FTD; vascular dementia, VD) underwent a complete diagnostic workup, including 3T-MRI and/or CT and CSF. Cortical atrophy was assessed with medial temporal atrophy (MTA), posterior atrophy (PA), and global cortical atrophy-frontal lobe (GCA-F) scales. BPSD were rated using the Neuropsychiatric Inventory (NPI), and BPSD clusters were defined according to the European Alzheimer Disease Consortium. link2 Results Delusions, hallucinations, and psychosis cluster were differently distributed among the diagnostic groups (p less then 0.05, p less then 0.001, and p lssociated with the occurrence and severity of BPSD in clinical practice. Longitudinal studies are however required to ascertain their actual predictive value.This review summarizes our current knowledge of human disease-relevant genetic variants within the family of voltage gated Ca2+ channels. Ca2+ channelopathies cover a wide spectrum of diseases including epilepsies, autism spectrum disorders, intellectual disabilities, developmental delay, cerebellar ataxias and degeneration, severe cardiac arrhythmias, sudden cardiac death, eye disease and endocrine disorders such as congential hyperinsulinism and hyperaldosteronism. A special focus will be on the rapidly increasing number of de novo missense mutations identified in the pore-forming α1-subunits with next generation sequencing studies of well-defined patient cohorts. In contrast to likely gene disrupting mutations these can not only cause a channel loss-of-function but can also induce typical functional changes permitting enhanced channel activity and Ca2+ signaling. Such gain-of-function mutations could represent therapeutic targets for mutation-specific therapy of Ca2+-channelopathies with existing or novel Ca2+-channel inhibitors. Moreover, many pathogenic mutations affect positive charges in the voltage sensors with the potential to form gating-pore currents through voltage sensors. If confirmed in functional studies, specific blockers of gating-pore currents could also be of therapeutic interest.Occlusions, restricted field of view and limited resolution all constrain a robot's ability to sense its environment from a single observation. In these cases, the robot first needs to actively query multiple observations and accumulate information before it can complete a task. In this paper, we cast this problem of active vision as active inference, which states that an intelligent agent maintains a generative model of its environment and acts in order to minimize its surprise, or expected free energy according to this model. We apply this to an object-reaching task for a 7-DOF robotic manipulator with an in-hand camera to scan the workspace. A novel generative model using deep neural networks is proposed that is able to fuse multiple views into an abstract representation and is trained from data by minimizing variational free energy. We validate our approach experimentally for a reaching task in simulation in which a robotic agent starts without any knowledge about its workspace. Each step, the next view pose is chosen by evaluating the expected free energy. link3 We find that by minimizing the expected free energy, exploratory behavior emerges when the target object to reach is not in view, and the end effector is moved to the correct reach position once the target is located. Similar to an owl scavenging for prey, the robot naturally prefers higher ground for exploring, approaching its target once located.Gaze and language are major pillars in multimodal communication. Gaze is a non-verbal mechanism that conveys crucial social signals in face-to-face conversation. However, compared to language, gaze has been less studied as a communication modality. The purpose of the present study is 2-fold (i) to investigate gaze direction (i.e., aversion and face gaze) and its relation to speech in a face-to-face interaction; and (ii) to propose a computational model for multimodal communication, which predicts gaze direction using high-level speech features. Twenty-eight pairs of participants participated in data collection. The experimental setting was a mock job interview. The eye movements were recorded for both participants. The speech data were annotated by ISO 24617-2 Standard for Dialogue Act Annotation, as well as manual tags based on previous social gaze studies. A comparative analysis was conducted by Convolutional Neural Network (CNN) models that employed specific architectures, namely, VGGNet and ResNet. The results showed that the frequency and the duration of gaze differ significantly depending on the role of participant.